Orientation of the Ig domains of CD8αβ relative to MHC class I

Lesley Devine, Jiaren Sun, Mark R. Barr, Paula B. Kavathas

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The cell surface glycoprotein CD8 functions as a coreceptor with the TCR for interaction with MHC class I. The cocrystal structure of the CD8αα-MHC complex showed that one CD8 Ig domain provided the majority of the contact with MHC class I and that residue R4 of that domain contacted the α2 domain of MHC class I. We previously showed by mutational analysis that this residue was critical for binding to MHC class I. To determine which of the Ig domains for the CD8αβ heterodimer would make the most contact with class I MHC, we expressed single-chain or dimeric forms of CD8 on COS-7 cells and measured the adhesion of MHC class I positive cells. We found that when one of the R4 residues was mutated in a CD8αα homodimer binding comparable to that of wild type was observed, whereas a double R4 mutant severely impaired binding. However, when mutant CD8α (R4K) was coexpressed with wild-type CD8β, binding was not observed. These results support the model in which it is CD8α, not CD8β, that is making the most of the contact with MHC class I, including the α2 domain. In addition, they demonstrate that a single-chain form of CD8αα can bind to MHC class I.

Original languageEnglish (US)
Pages (from-to)846-851
Number of pages6
JournalJournal of Immunology
Volume162
Issue number2
StatePublished - Jan 15 1999
Externally publishedYes

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COS Cells
Membrane Glycoproteins
Cell Adhesion
Immunoglobulin Domains

ASJC Scopus subject areas

  • Immunology

Cite this

Devine, L., Sun, J., Barr, M. R., & Kavathas, P. B. (1999). Orientation of the Ig domains of CD8αβ relative to MHC class I. Journal of Immunology, 162(2), 846-851.

Orientation of the Ig domains of CD8αβ relative to MHC class I. / Devine, Lesley; Sun, Jiaren; Barr, Mark R.; Kavathas, Paula B.

In: Journal of Immunology, Vol. 162, No. 2, 15.01.1999, p. 846-851.

Research output: Contribution to journalArticle

Devine, L, Sun, J, Barr, MR & Kavathas, PB 1999, 'Orientation of the Ig domains of CD8αβ relative to MHC class I', Journal of Immunology, vol. 162, no. 2, pp. 846-851.
Devine L, Sun J, Barr MR, Kavathas PB. Orientation of the Ig domains of CD8αβ relative to MHC class I. Journal of Immunology. 1999 Jan 15;162(2):846-851.
Devine, Lesley ; Sun, Jiaren ; Barr, Mark R. ; Kavathas, Paula B. / Orientation of the Ig domains of CD8αβ relative to MHC class I. In: Journal of Immunology. 1999 ; Vol. 162, No. 2. pp. 846-851.
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