Structural evidence of T cell xeno-reactivity in the absence of molecular mimicry.
The T cell receptor (TCR), from a xeno-reactive murine cytotoxic T lymphocyte clone AHIII12.2, recognizes murine H-2Db complexed with peptide p1027 (FAPGVFPYM), as well as human HLA-A2.1 complexed with peptide p1049 (ALWGFFPVL). A commonly proposed model (the molecular mimicry model) used to explain TCR cross-reactivity suggests that the molecular surfaces of the recognized complexes are similar in shape, charge, or both, in spite of the primary sequence differences. To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and Db/p1027 to 2.5 A and 2.8 A resolution, respectively. The crystal structures show that the TCR footprint regions of the two class I complexes are significantly different in shape and charge. We propose that rather than simple molecular mimicry, unpredictable arrays of common and differential contacts on the two class I complexes are used for their recognition by the same TCR.
Zhao
R
R
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Loftus
D J
DJ
Appella
E
E
Collins
E J
EJ
D000818:Animals; D002999:Clone Cells / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology*; D018360:Crystallography, X-Ray; D006183:H-2 Antigens / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006183:H-2 Antigens; D006680:HLA Antigens; D064532:Histocompatibility Antigen H-2D; D010455:Peptides; D011948:Receptors, Antigen, T-Cell