Peptide length variants p2Ca and QL9 present distinct conformations to L(d)-specific T cells.
Recent advances have provided insights into how the TCR interacts with MHC/peptide complexes and a rationale to predict optimal epitopes for MHC binding and T cell recognition. For example, peptides of nine residues are predicted to be optimal for binding to H2-L(d), although 8 mer epitopes have also been identified. It has been predicted that 8 mer and 9 mer length variant peptides bound to L(d) present identical epitopes to T cells. However, in contrast to this prediction, we demonstrate here that the 8 mer peptide p2Ca and its 9 mer length variant QL9, extended by an N-terminal glutamine, assume distinct conformations when bound to L(d). We generated self-L(d)-restricted CTL clones specific for p2Ca that recognize L(d)/QL9 poorly if at all. This result is in sharp contrast to what has been observed with L(d)-alloreactive T cells that possess a much higher affinity for L(d)/QL9 than for L(d)/p2Ca. Alanine substitutions of the N-terminal residues of the QL9 peptide rescue detection by these self-L(d)/p2Ca-specific T cells, but decrease recognition by the L(d)-alloreactive 2C T cell clone. In addition, 2C T cell recognition of the p2Ca peptide is affected by different alanine substitutions compared with 2C T cell recognition of the QL9 peptide. These data clearly demonstrate that the p2Ca and QL9 peptides assume distinct conformations when bound to L(d) and, furthermore, demonstrate that there is flexibility in peptide binding within the MHC class I cleft.
Hornell
T M
TM
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Martin
S M
SM
Myers
N B
NB
Connolly
J M
JM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology*; D006183:H-2 Antigens / Q000737:chemistry / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D009842:Oligopeptides; C440022:QL9 peptide; C088354:p2Ca peptide