A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2

Russell D. Salter; Richard J. Benjamin; Pamela K. Wesley; Sarah E. Buxton; Thomas P J Garrett; Carol Clayberger; Alan M. Krensky; Anne M. Norment; Dan R. Littman; Peter Parham

doi:10.1038/345041a0

A binding site for the T-cell co-receptor CD8 on the α₃ domain of HLA-A2

Russell D. Salter^*, Richard J. Benjamin, Pamela K. Wesley, Sarah E. Buxton, Thomas P J Garrett, Carol Clayberger, Alan M. Krensky, Anne M. Norment, Dan R. Littman, Peter Parham

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

535 Scopus citations

Abstract

Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 α-chain binds to the α₃ domain of HLA-A2.1. Three clusters of α₃ residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.

Original language	English (US)
Pages (from-to)	41-46
Number of pages	6
Journal	Nature
Volume	345
Issue number	6270
DOIs	https://doi.org/10.1038/345041a0
State	Published - 1990

ASJC Scopus subject areas

General

Access to Document

10.1038/345041a0

Cite this

@article{527efcfdfc3748ff9c4d39780a01a4fa,

title = "A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2",

abstract = "Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 α-chain binds to the α3 domain of HLA-A2.1. Three clusters of α3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.",

author = "Salter, {Russell D.} and Benjamin, {Richard J.} and Wesley, {Pamela K.} and Buxton, {Sarah E.} and Garrett, {Thomas P J} and Carol Clayberger and Krensky, {Alan M.} and Norment, {Anne M.} and Littman, {Dan R.} and Peter Parham",

year = "1990",

doi = "10.1038/345041a0",

language = "English (US)",

volume = "345",

pages = "41--46",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "6270",

}

TY - JOUR

T1 - A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2

AU - Salter, Russell D.

AU - Benjamin, Richard J.

AU - Wesley, Pamela K.

AU - Buxton, Sarah E.

AU - Garrett, Thomas P J

AU - Clayberger, Carol

AU - Krensky, Alan M.

AU - Norment, Anne M.

AU - Littman, Dan R.

AU - Parham, Peter

PY - 1990

Y1 - 1990

N2 - Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 α-chain binds to the α3 domain of HLA-A2.1. Three clusters of α3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.

AB - Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 α-chain binds to the α3 domain of HLA-A2.1. Three clusters of α3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.

UR - http://www.scopus.com/inward/record.url?scp=0025366452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025366452&partnerID=8YFLogxK

U2 - 10.1038/345041a0

DO - 10.1038/345041a0

M3 - Article

C2 - 2109837

AN - SCOPUS:0025366452

SN - 0028-0836

VL - 345

SP - 41

EP - 46

JO - Nature

JF - Nature

IS - 6270

ER -

A binding site for the T-cell co-receptor CD8 on the α₃ domain of HLA-A2

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this