A beta polymorphic residues responsible for class II molecule recognition by alloreactive T cells.
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.
Buerstedde
J M
JM
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
Nilson
A E
AE
Chase
C G
CG
Bell
M P
MP
Beck
B N
BN
Pease
L R
LR
McKean
D J
DJ
D000483:Alleles; D000595:Amino Acid Sequence; D001402:B-Lymphocytes; D003001:Cloning, Molecular; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007126:Immunoglobulin Allotypes / Q000235:genetics / Q000276:immunology; D008223:Lymphoma; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes; D011948:Receptors, Antigen, T-Cell