CD8B

Summary

CD8B (CD8 subunit beta, HGNC:1707) is a protein-coding gene on chromosome 2p11.2, encoding T-cell surface glycoprotein CD8 beta chain (P10966). Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses.

The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 beta chain isoforms. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified.

Source: NCBI Gene 926 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_004931

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1707
Approved symbol	CD8B
Name	CD8 subunit beta
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	Ly-3, LYT3, P37, CD8beta
Ensembl gene	ENSG00000172116
Ensembl biotype	protein_coding
OMIM	186730
Entrez	926

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000331469, ENST00000349455, ENST00000390655, ENST00000393759, ENST00000393761, ENST00000431506, ENST00000896816, ENST00000939902

RefSeq mRNA: 5 — MANE Select: NM_004931 NM_001178100, NM_004931, NM_172101, NM_172102, NM_172213

CCDS: CCDS1994, CCDS1995, CCDS1997, CCDS42708, CCDS54376

Canonical transcript exons

ENST00000390655 — 6 exons

Exon	Start	End
ENSE00001923197	86861823	86861886
ENSE00001940681	86838167	86842319
ENSE00002451497	86844922	86844958
ENSE00002475314	86852997	86853086
ENSE00002506201	86858057	86858416
ENSE00002516827	86846684	86846773

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 90.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2533 / max 45.1090, expressed in 36 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29581	0.2533	36

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	90.83	gold quality
blood	UBERON:0000178	85.15	gold quality
thymus	UBERON:0002370	83.75	gold quality
lymph node	UBERON:0000029	81.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.15	gold quality
spleen	UBERON:0002106	77.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.13	gold quality
vermiform appendix	UBERON:0001154	76.09	gold quality
small intestine	UBERON:0002108	74.19	gold quality
gall bladder	UBERON:0002110	73.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.03	silver quality
adenohypophysis	UBERON:0002196	71.76	gold quality
bone marrow	UBERON:0002371	71.46	gold quality
calcaneal tendon	UBERON:0003701	70.68	gold quality
caecum	UBERON:0001153	70.09	gold quality
pituitary gland	UBERON:0000007	69.41	gold quality
right uterine tube	UBERON:0001302	68.91	gold quality
rectum	UBERON:0001052	68.04	gold quality
mucosa of transverse colon	UBERON:0004991	68.02	gold quality
colonic epithelium	UBERON:0000397	67.88	gold quality
bone marrow cell	CL:0002092	67.50	silver quality
body of stomach	UBERON:0001161	66.28	gold quality
jejunal mucosa	UBERON:0000399	65.56	gold quality
upper lobe of left lung	UBERON:0008952	65.10	gold quality
upper lobe of lung	UBERON:0008948	64.40	gold quality
endocervix	UBERON:0000458	63.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	62.87	gold quality
stomach	UBERON:0000945	62.84	gold quality
endometrium epithelium	UBERON:0004811	62.60	gold quality
right coronary artery	UBERON:0001625	62.24	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-CURD-84	yes	2029.20
E-CURD-79	yes	1786.54
E-MTAB-6505	yes	1719.69
E-CURD-95	yes	1450.93
E-CURD-120	yes	1253.17
E-CURD-77	yes	1031.37
E-CURD-55	yes	960.73
E-HCAD-4	yes	711.70
E-CURD-89	yes	688.90
E-ANND-5	yes	592.49
E-MTAB-8207	yes	537.62
E-CURD-88	yes	524.96
E-CURD-122	yes	58.48
E-HCAD-1	yes	56.97
E-HCAD-8	yes	50.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREM, GATA3, SATB1

Literature-anchored findings (GeneRIF, showing 12)

• A clustering of DNase hypersensitivity sites and matrix attachment regions capable of binding SATB1 and GATA-3, colocalized at the 3’ end of the CD8B gene, suggests that this region is an epigenetic regulator of CD8 expression. (PMID:11937547)
• RT-PCR, and related methodologies are not useful substitutes for assessment of CD4 and CD8 cell numbers in HIV-infected persons. (PMID:12702212)
• study demonstrated differential mRNA expression patterns of CD8beta splice variants in thymocytes and in resting, memory, and activated primary CD8(+) T cells (PMID:18490743)
• Data show that CD8+LAP+ cells produce IFN-gamma, and these cells suppress EAE that is dependent on both TGF-beta and IFN-gamma. (PMID:19768696)
• [review] Coreceptor CD8alphabeta contributes to the antigen-recognition process by binding to a largely invariant region of the MHCI molecule and by promoting intracellular signaling. (PMID:21954283)
• Nef-mediated down-modulation of CD8alphabeta is a fundamental property of primate lentiviruses. (PMID:22013062)
• transcription factor cAMP-responsive element modulator alpha (CREMalpha), which is expressed at increased levels in T cells from systemic lupus erythematosus patients, contributes to transcriptional silencing of CD8A and CD8B. (PMID:24047902)
• CREMalpha orchestrates epigenetic remodeling of the CD8A,B through the recruitment of DNA methyltransferase (DNMT) 3a and histone methyltransferase G9a. (PMID:24297179)
• Endometrioid endometrial carcinomas are capable of down-regulating CD8 expression by cytotoxic T lymphocytes. (PMID:27346574)
• results suggest that mycoplasma induces a resistance to multiple drugs in hepatocarcinoma cells which required the interaction of P37 and Annexin A2. The pathway downstream this interaction needs to be explored (PMID:28976984)
• CD45RA, CD8beta, and IFNgamma Are Potential Immune Biomarkers of Human Cognitive Function. (PMID:33324408)
• Experimental colitis promotes sustained, sex-dependent, T-cell-associated neuroinflammation and parkinsonian neuropathology. (PMID:34412704)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd8b	ENSDARG00000058682
mus_musculus	Cd8b1	ENSMUSG00000053044
rattus_norvegicus	Cd8b	ENSRNOG00000007129

Paralogs (1): CD8B2 (ENSG00000254126)

Protein

Protein identifiers

T-cell surface glycoprotein CD8 beta chain — P10966 (reviewed: P10966)

All UniProt accessions (2): P10966, E9PD41

UniProt curated annotations — full annotation on UniProt →

Function. Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. A palmitoylation site in the cytoplasmic tail of CD8B chain contributes to partitioning of CD8 into the plasma membrane lipid rafts where signaling proteins are enriched. Once LCK recruited, it initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). Additionally, plays a critical role in thymic selection of CD8+ T-cells.

Subunit / interactions. Forms disulfide-linked heterodimers with CD8A at the cell surface. Interacts with CD3D; this interaction couples TCR-CD3 with CD8. Interacts with LCK.

Subcellular location. Cell membrane Cell membrane Secreted Cell membrane Cell membrane Secreted Secreted Secreted.

Tissue specificity. Isoform 1, isoform 3, isoform 5, isoform 6, isoform 7 and isoform 8 are expressed in both thymus and peripheral CD8+ T-cells. Expression of isoform 1 is higher in thymus CD8+ T-cells than in peripheral CD8+ T-cells. Expression of isoform 6 is higher in peripheral CD8+ T-cells than in thymus CD8+ T-cells.

Post-translational modifications. Phosphorylated as a consequence of T-cell activation. Palmitoylated at the cytoplasmic tail and thereby targets the heterodimer CD8A/CD8B to lipid rafts unlike CD8A homodimers.

Isoforms (8)

UniProt ID	Names	Canonical?
P10966-1	1, M-1, Mbeta1	yes
P10966-2	2, M-3, Mbeta2
P10966-3	3, S-1, Sbeta3
P10966-4	4, M-2
P10966-6	5, Mbeta3
P10966-7	6, Sbeta1
P10966-8	7, Sbeta4
P10966-9	8, Sbeta5

RefSeq proteins (5): NP_001171571, NP_004922, NP_742099, NP_742100, NP_757362 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR042414	CD8B	Family

Pfam: PF07686

UniProt features (18 total): splice variant 6, sequence conflict 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, modified residue 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10966-F1	82.03	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 209

Disulfide bonds (1): 41–116

Glycosylation sites (1): 102

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-182218	Nef Mediated CD8 Down-regulation
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-162906	HIV Infection
R-HSA-162909	Host Interactions of HIV factors
R-HSA-1643685	Disease
R-HSA-164938	Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
R-HSA-164952	The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-168256	Immune System
R-HSA-5663205	Infectious disease
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 269 (showing top): MORF_RAGE, CHIBA_RESPONSE_TO_TSA_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_45, MODULE_64, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS, MODULE_16, GOBP_REGULATION_OF_IMMUNE_RESPONSE, REACTOME_NEF_MEDIATES_DOWN_MODULATION_OF_CELL_SURFACE_RECEPTORS_BY_RECRUITING_THEM_TO_CLATHRIN_ADAPTERS, GCM_RING1, MODULE_75, REACTOME_HIV_INFECTION, MORF_FANCG

GO Biological Process (7): adaptive immune response (GO:0002250), immune response (GO:0006955), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), T cell activation (GO:0042110), T cell receptor signaling pathway (GO:0050852), immune system process (GO:0002376), regulation of immune response (GO:0050776)

GO Molecular Function (3): coreceptor activity (GO:0015026), MHC class I protein binding (GO:0042288), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), early endosome membrane (GO:0031901), T cell receptor complex (GO:0042101), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1
Adaptive Immune System	1
Immune System	1
Viral Infection Pathways	1
HIV Infection	1
The role of Nef in HIV-1 replication and disease pathogenesis	1
Host Interactions of HIV factors	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
immune response	2
immune system process	1
response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
lymphocyte activation	1
antigen receptor-mediated signaling pathway	1
biological_process	1
regulation of immune system process	1
regulation of response to stimulus	1
signaling receptor activity	1
MHC protein binding	1
binding	1
membrane	1
cell periphery	1
early endosome	1
endosome membrane	1
plasma membrane signaling receptor complex	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
CD8B	PRSS2	psi-mi:“MI:0914”(association)	0.350
CD8B	KLRG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): CD8B (Co-localization), TMEM214 (Affinity Capture-MS), KLRG2 (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ERGIC2 (Affinity Capture-MS), TMED8 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), PRSS2 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), SRC (Affinity Capture-MS), SORT1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), SBDS (Affinity Capture-MS)

ESM2 similar proteins: A6NJW9, O02757, P01730, P01731, P01732, P05541, P07725, P09793, P0DSE1, P10300, P10747, P10966, P15530, P16003, P16004, P16410, P30433, P30434, P31041, P31042, P31043, P31783, P33705, P33706, P40259, P41688, P42069, P42072, P50283, P79184, P79336, Q08338, Q08340, Q28071, Q2YFS1, Q2YFS2, Q2YFS3, Q3LRV9, Q495A1, Q5JXA9

Diamond homologs: A0A1B0GX68, A6NJW9, P01735, P05541, P06321, P10300, P10966, P30434, P79336, Q9XSM7, A0A075B6L6, A0A075B6N1, A0A075B6N3, A0A075B6N4, A0A087WV62, A0A0A0MRZ8, A0A0A0MS03, A0A0A0MS05, A0A0A0MS06, A0A0A6YYD4, A0A0B4J1U6, A0A0B4J241, A0A0B4J274, A0A0B4J2E0, A0A0C4DH25, A0A0C4DH55, A0A0C4DH59, A0A0K0K1C0, A0A0K0K1G6, A0A1B0GX49, A0A1B0GX51, A0A1B0GX78, A0A1B0GXF2, A0A539, A0A576, A0A577, A0A578, A0A584, A0A589, A0A597

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1101 predictions. Top by Δscore:

Variant	Effect	Δscore
2:86844920:A:AC	donor_gain	1.0000
2:86844921:C:CC	donor_gain	1.0000
2:86846682:A:AC	donor_gain	1.0000
2:86846683:C:CC	donor_gain	1.0000
2:86846683:CAGCA:C	donor_gain	1.0000
2:86852990:AACTC:A	donor_loss	1.0000
2:86852991:ACTC:A	donor_loss	1.0000
2:86852992:CTCA:C	donor_loss	1.0000
2:86852993:TCA:T	donor_loss	1.0000
2:86852994:CACC:C	donor_loss	1.0000
2:86852995:A:AG	donor_loss	1.0000
2:86852995:AC:A	donor_gain	1.0000
2:86852996:CC:C	donor_gain	1.0000
2:86852996:CCCTT:C	donor_gain	1.0000
2:86853083:TCAA:T	acceptor_gain	1.0000
2:86853084:CAA:C	acceptor_gain	1.0000
2:86853084:CAAC:C	acceptor_gain	1.0000
2:86853087:C:CC	acceptor_gain	1.0000
2:86858066:G:C	donor_gain	1.0000
2:86858078:T:TA	donor_gain	1.0000
2:86858079:C:A	donor_gain	1.0000
2:86858417:C:CC	acceptor_gain	1.0000
2:86861818:CTTAC:C	donor_loss	1.0000
2:86861819:TTACC:T	donor_loss	1.0000
2:86861820:TACCT:T	donor_loss	1.0000
2:86861821:A:AC	donor_gain	1.0000
2:86861822:C:CC	donor_gain	1.0000
2:86861822:C:CT	donor_loss	1.0000
2:86815720:T:C	acceptor_gain	0.9900
2:86815720:T:TC	acceptor_gain	0.9900

AlphaMissense

1361 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:86858298:C:A	W54C	0.986
2:86858298:C:G	W54C	0.986
2:86858082:G:C	F126L	0.981
2:86858082:G:T	F126L	0.981
2:86858084:A:G	F126L	0.981
2:86858120:A:C	Y114D	0.980
2:86858113:C:G	C116S	0.979
2:86858114:A:T	C116S	0.979
2:86858113:C:T	C116Y	0.978
2:86858114:A:G	C116R	0.977
2:86858112:G:C	C116W	0.976
2:86858292:T:A	R56S	0.973
2:86858292:T:G	R56S	0.973
2:86858158:A:G	L101P	0.971
2:86858300:A:G	W54R	0.969
2:86858300:A:T	W54R	0.969
2:86858152:A:G	L103P	0.965
2:86858119:T:C	Y114C	0.964
2:86858293:C:G	R56T	0.963
2:86858065:A:G	L132P	0.962
2:86858253:G:C	F69L	0.958
2:86858253:G:T	F69L	0.958
2:86858255:A:G	F69L	0.958
2:86858338:C:G	C41S	0.956
2:86858339:A:T	C41S	0.956
2:86858113:C:A	C116F	0.954
2:86858125:C:A	G112V	0.954
2:86858296:A:G	L55P	0.954
2:86858114:A:C	C116G	0.949
2:86858115:G:C	F115L	0.948

dbSNP variants (sampled 300 via entrez): RS1000124020 (2:86823158 G>A), RS1000196443 (2:86817669 A>G), RS1000228309 (2:86861766 C>G,T), RS1000315550 (2:86837671 C>T), RS1000375376 (2:86816018 T>A,C), RS1000422295 (2:86855473 C>T), RS1000483999 (2:86863069 T>C), RS1000571963 (2:86829675 T>C), RS1000576106 (2:86823010 T>C), RS1000622518 (2:86857038 G>C,T), RS1000689651 (2:86829398 C>T), RS1001114027 (2:86843699 G>T), RS1001207448 (2:86856794 C>A,G,T), RS1001248515 (2:86851137 T>C), RS1001329057 (2:86838886 T>G)

Disease associations

OMIM: gene MIM:186730 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001116_5	Progressive supranuclear palsy	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	3
Nickel	increases expression	2
VX-agent	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases expression	1
benzo(e)pyrene	affects methylation	1
monomethylpropion	increases expression	1
2-palmitoylglycerol	increases expression	1
clothianidin	increases expression	1
Fluorouracil	affects response to substance, decreases expression	1
Manganese	increases expression	1
Methapyrilene	affects methylation	1
Tobacco Smoke Pollution	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.