Alloreactive T cells respond specifically to multiple distinct peptide-MHC complexes.
The molecular basis underlying the specificity of alloreactive T cells for peptide-major histocompatibility complex ligands has been elusive. Here we describe a screen of 60 I-E(k)-alloreactive T cells and 83 naturally processed peptides that identified 9 reactive T cells. Three of the T cells responded to multiple, distinct peptides that shared no sequence homology. These T cells recognized each peptide-major histocompatibility complex ligand specifically and used a distinct constellation of I-E(k) contact residues for each interaction. Our studies show that alloreactive T cells have a 'germline-encoded' capacity to recognize multiple, distinct ligands and thus show 'polyspecificity', not degeneracy. Our findings help to explain the high frequency of alloreactive T cells and provide insight into the nature of T cell specificity.
Felix
Nathan J
NJ
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63130, USA.
Donermeyer
David L
DL
Horvath
Stephen
S
Walters
James J
JJ
Gross
Michael L
ML
Suri
Anish
A
Allen
Paul M
PM
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell