RT Journal Article
SR Electronic
T1 Dominant TCR-α Requirements for a Self Antigen Recognition in Humans
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 6253
OP 6260
DO 10.4049/jimmunol.169.11.6253
VO 169
IS 11
A1 Mantovani, Stefania
A1 Palermo, Belinda
A1 Garbelli, Silvia
A1 Campanelli, Rita
A1 Robustelli della Cuna, Gioacchino
A1 Gennari, Roberto
A1 Benvenuto, Federica
A1 Lantelme, Erica
A1 Giachino, Claudia
YR 2002
UL http://www.jimmunol.org/content/169/11/6253.abstract
AB TCR-α and -β chains are composed of somatically rearranged V, D, and J germline-encoded gene segments that confer Ag specificity. Recent crystallographic analyses revealed that TCR-α has more contacts with peptide than TCR-β, suggesting the possibility that peptide recognition predominantly relies on TCR-α. T cells specific for the self Ag Melan-A/MART-1 possess an exceptionally high precursor frequency in human histocompatibility leukocyte Ag-A2 individuals. This provided a unique situation for assessment of the structural relationship between TCR and peptide/MHC ligand at both the pre- and postimmune levels. Molecular and phenotypic analysis of many different Melan-A-specific T cell populations revealed that a structural constraint is imposed on the TCR for engagement with Melan-A peptides presented by HLA-A2, namely the highly preferential use of a particular TCRAV segment, AV2. Examination of CD8 single-positive thymocytes indicated that this preferential use in forming the Melan-A-specific TCR is mainly imposed by intrathymic positive selection. Our data demonstrate a dominant function of TCRAV2 segment in forming the TCR repertoire specific for the human self Ag Melan-A/MART-1 and support the view that Ag recognition is mediated predominantly by TCR-α.