Alloreactive and syngeneic CTL are comparably dependent on interaction with MHC class I alpha-helical residues.
The molecular basis for the difference in the strength of T cell responses to self vs alloantigens is unknown, but may reflect how T cells are selected in the thymus. Because T cells with a high affinity for foreign as opposed to self MHC molecules are able to mature, it has been proposed that alloreactive T cells may be more strongly dependent upon interaction with MHC residues than are self-restricted T cells. This study was undertaken to rigorously address this hypothesis. Whereas other studies have compared self vs alloantigen recognition of different MHC alleles by a single T cell clone, we have compared self vs alloantigen recognition of a single MHC allele, H-2Ld, by a large panel of self-restricted and alloreactive T cell clones. Target cells expressing Ld molecules mutated at several different potential TCR contact residues were analyzed to determine which residues are important for recognition by self-restricted vs alloreactive T cells. We unequivocally demonstrate that self-restricted and alloreactive T cells do not differ, but rather are comparably dependent on interaction with MHC residues. Importantly, both self-restricted and alloreactive T cells are dependent upon the same MHC residues as primary contacts and, in addition, share a common recognition pattern of Ld. Furthermore, our analysis enables us to provide a model for allotype-specific T cell recognition of Ld vs Kb class I molecules.
Hornell
T M
TM
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Solheim
J C
JC
Myers
N B
NB
Gillanders
W E
WE
Balendiran
G K
GK
Hansen
T H
TH
Connolly
J M
JM
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017433:Protein Structure, Secondary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta