Positive selection of an H2-M3 restricted T cell receptor.
Thymocytes are positively selected for alphabeta T cell antigen receptors (TCR) that recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. MHC bound peptides participate in positive selection; however, their role has remained controversial. A TCR transgenic mouse was established using a TCR restricted to the MHC class Ib molecule, H2-M3. Having defined H2-M3 as the positively selecting MHC molecule, the severely limited number of H2-M3 binding peptides allowed us to characterize an NADH dehydrogenase subunit 1 (ND1)-derived peptide as the physiological ligand of positive selection. This peptide bears no apparent sequence homology to the cognate peptide, is expressed ubiquitously, and yet does not interfere with peripheral T cells. Our studies also suggest that positive selection becomes promiscuous at high epitope densities.
Berg
R E
RE
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Princiotta
M F
MF
Irion
S
S
Moticka
J A
JA
Dahl
K R
KR
Staerz
U D
UD
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002460:Cell Line; D003433:Crosses, Genetic; D005333:Fetus; D006183:H-2 Antigens / Q000235:genetics* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009239:N-Formylmethionine / Q000276:immunology / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000276:immunology / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D009924:Organ Culture Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006183:H-2 Antigens; C078177:H2-M3 antigen; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D009239:N-Formylmethionine; D009245:NADH Dehydrogenase