A(β) polymorphic residues responsible for class II molecule recognition by alloreactive T cells

J. M. Buerstedde, A. E. Nilson, C. G. Chase, M. P. Bell, B. N. Beck, L. R. Pease, D. J. McKean

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21 Scopus citations

Abstract

In an effort to characterize the ligand that is bound by T helper lymphocyte antigen receptors, we have begun to identify class II polymorphic residues that comprise part of the allospecific TCR binding sites. Site-directed mutagenesis was used to construct mutant A(β)(k) (A(β)(k)*) genes that encode polypeptides into which single or multiple residues of the A(β)(d) polypeptide have been substituted in the β1 domain. A panel of cloned cell lines expressing the mutant A(β)(k)* A(α)(k) or A(β)(k)* A(α)(d) molecules was analyzed for the ability to stimulate A(k) or A(d) alloreactive T cell hybridomas. Substitution of d for k residues at specific positions in the β1 domain resulted not only in the loss of epitopes recognized by A(k)-reactive T cells but, more importantly, in the gain of epitopes recognized by A(d)-reactive T cells. Some of the polymorphic residues identified as contributing to the T cell epitopes are the same residues that contribute to the serologically immunodominant epitope. Other T cell epitopes map to positions predicted to be located either in an α-helix forming one side, or in a β-pleated sheet forming the bottom of the putative antigen binding site. Thus, unlike serologic epitopes, TCR epitopes can be determined by A(β) polymorphic residues in many different regions of the β1 domain and frequently depend upon contributions of A(α) polymorphic residues.

Original languageEnglish (US)
Pages (from-to)1645-1654
Number of pages10
JournalJournal of Experimental Medicine
Volume169
Issue number5
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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