TY - JOUR
T1 - A basis for alloreactivity
T2 - MHC helical residues broaden peptide recognition by the TCR
AU - Daniel, Claude
AU - Horvath, Stephen
AU - Allen, Paul M.
N1 - Funding Information:
We thank Jerri Smith for her assistance in the preparation of this manuscript. We thank members of our laboratory and colleagues for their helpful comments. This work was supported by grants from the National Institutes of Health. C. D. was supported by a fellowship from the Natural Sciences and Engineering Research Council of Canada.
PY - 1998/5
Y1 - 1998/5
N2 - The high frequency of alloreactive T cells is a major hindrance for transplantation; however, the molecular basis for alloreactivity remains elusive. We examined the I-E(p) alloreactivity of a well-characterized Hb(64- 76)/I-E(k)-specific murine T cell. Using a combinatorial peptide library approach, we identified a highly stimulatory alloepitope mimic and observed that the recognition of the central TCR contact residues (P3 and P5) was much more flexible than that seen with Hb(64-76)/I-E(k), but still specific. Therefore, alloreactive T cells can recognize a self-peptide/MHC surface; however, the allogeneic MHC molecule changes the recognition requirements for the central region of the peptide, allowing a more diverse repertoire of ligands to be recognized.
AB - The high frequency of alloreactive T cells is a major hindrance for transplantation; however, the molecular basis for alloreactivity remains elusive. We examined the I-E(p) alloreactivity of a well-characterized Hb(64- 76)/I-E(k)-specific murine T cell. Using a combinatorial peptide library approach, we identified a highly stimulatory alloepitope mimic and observed that the recognition of the central TCR contact residues (P3 and P5) was much more flexible than that seen with Hb(64-76)/I-E(k), but still specific. Therefore, alloreactive T cells can recognize a self-peptide/MHC surface; however, the allogeneic MHC molecule changes the recognition requirements for the central region of the peptide, allowing a more diverse repertoire of ligands to be recognized.
UR - http://www.scopus.com/inward/record.url?scp=0032076237&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80559-2
DO - 10.1016/S1074-7613(00)80559-2
M3 - Article
C2 - 9620675
AN - SCOPUS:0032076237
SN - 1074-7613
VL - 8
SP - 543
EP - 552
JO - Immunity
JF - Immunity
IS - 5
ER -