TY - JOUR
T1 - Alloreactive and syngeneic CTL are comparably dependent on interaction with MHC class I α-helical residues
AU - Hornell, Tara M.C.
AU - Solheim, Joyce C.
AU - Myers, Nancy B.
AU - Gillanders, William E.
AU - Balendiran, Ganesaratnam K.
AU - Hansen, Ted H.
AU - Connolly, Janet M.
PY - 1999/9/15
Y1 - 1999/9/15
N2 - 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- 2L(d), by a large panel of self-restricted and alloreactive T cell clones. Target cells expressing L(d) 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 L(d). Furthermore, our analysis enables us to provide a model for allotype-specific T cell recognition of L(d) vs Kb class I molecules.
AB - 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- 2L(d), by a large panel of self-restricted and alloreactive T cell clones. Target cells expressing L(d) 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 L(d). Furthermore, our analysis enables us to provide a model for allotype-specific T cell recognition of L(d) vs Kb class I molecules.
UR - http://www.scopus.com/inward/record.url?scp=0033568276&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.163.6.3217
DO - 10.4049/jimmunol.163.6.3217
M3 - Article
C2 - 10477590
AN - SCOPUS:0033568276
SN - 0022-1767
VL - 163
SP - 3217
EP - 3225
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -