Journal of Experimental Medicine, Vol 169, 1645-1654, Copyright © 1989 by Rockefeller University Press

ARTICLES

A beta polymorphic residues responsible for class II molecule recognition by alloreactive T cells

JM Buerstedde, AE Nilson, CG Chase, MP Bell, BN Beck, LR Pease and DJ McKean
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.

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 Ak beta (Ak beta*) genes that encode polypeptides into which single or multiple residues of the Ad beta polypeptide have been substituted in the beta 1 domain. A panel of cloned cell lines expressing the mutant Ak beta* Ak alpha or Ak beta* Ad alpha molecules was analyzed for the ability to stimulate Ak or Ad alloreactive T cell hybridomas. Substitution of d for k residues at specific positions in the beta 1 domain resulted not only in the loss of epitopes recognized by Ak-reactive T cells but, more importantly, in the gain of epitopes recognized by Ad-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 alpha-helix forming one side, or in a beta-pleated sheet forming the bottom of the putative antigen binding site. Thus, unlike serologic epitopes, TCR epitopes can be determined by A beta polymorphic residues in many different regions of the beta 1 domain and frequently depend upon contributions of A alpha polymorphic residues.
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This article has been cited by other articles:

• Dellabona, P., Peccoud, J., Benoist, C., Mathis, D. (1989). T-cell Recognition of Superantigens: Inside or Outside the Groove?. Cold Spring Harb Symp Quant Biol 54: 375-381 [Abstract]  
• Berzofsky, J.A., Kurata, A., Takahashi, H., Brett, S.J., McKean, D.J. (1989). Molecular Studies of Antigen Processing and Presentation to T Cells by Class II MHC Molecules. Cold Spring Harb Symp Quant Biol 54: 417-430 [Abstract]  

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