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, Larry R Pease, D. J. McKean

Research output: Contribution to journalArticle

21 Citations (Scopus)

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
StatePublished - 1989

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Epitopes
T-Lymphocytes
T-Lymphocyte Epitopes
Binding Sites
Immunodominant Epitopes
Peptides
Antigen Receptors
Hybridomas
Helper-Inducer T-Lymphocytes
Site-Directed Mutagenesis
Ligands
Antigens
Cell Line
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Buerstedde, J. M., Nilson, A. E., Chase, C. G., Bell, M. P., Beck, B. N., Pease, L. R., & McKean, D. J. (1989). A(β) polymorphic residues responsible for class II molecule recognition by alloreactive T cells. Journal of Experimental Medicine, 169(5), 1645-1654.

A(β) polymorphic residues responsible for class II molecule recognition by alloreactive T cells. / Buerstedde, J. M.; Nilson, A. E.; Chase, C. G.; Bell, M. P.; Beck, B. N.; Pease, Larry R; McKean, D. J.

In: Journal of Experimental Medicine, Vol. 169, No. 5, 1989, p. 1645-1654.

Research output: Contribution to journalArticle

Buerstedde, JM, Nilson, AE, Chase, CG, Bell, MP, Beck, BN, Pease, LR & McKean, DJ 1989, 'A(β) polymorphic residues responsible for class II molecule recognition by alloreactive T cells', Journal of Experimental Medicine, vol. 169, no. 5, pp. 1645-1654.
Buerstedde, J. M. ; Nilson, A. E. ; Chase, C. G. ; Bell, M. P. ; Beck, B. N. ; Pease, Larry R ; McKean, D. J. / A(β) polymorphic residues responsible for class II molecule recognition by alloreactive T cells. In: Journal of Experimental Medicine. 1989 ; Vol. 169, No. 5. pp. 1645-1654.
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