TCR-alpha CDR3 loop audition regulates positive selection.
How positive selection molds the T cell repertoire has been difficult to examine. In this study, we use TCR-beta-transgenic mice in which MHC shapes TCR-alpha use. Differential AV segment use is directly related to the constraints placed on the composition of the CDR3 loops. Where these constraints are low, efficient selection of alphabeta pairs follows. This mode of selection preferentially uses favored AV-AJ rearrangements and promotes diversity. Increased constraint on the alpha CDR3 loops leads to inefficient selection associated with uncommon recombination events and limited diversity. Further, the two modes of selection favor alternate sets of AJ segments. We discuss the relevance of these findings to the imprint of self-MHC restriction and peripheral T cell activation.
Ferreira
Cristina
C
Transplantation Biology Group, Department of Immunology, Imperial College, Hammersmith Hospital, Du Cane Road, London, United Kingdom.
Furmanski
Anna
A
Millrain
Maggie
M
Bartok
Istvan
I
Guillaume
Philippe
P
Lees
Rosemary
R
Simpson
Elizabeth
E
MacDonald
H Robson
HR
Dyson
Julian
J
D000818:Animals; D002478:Cells, Cultured; D017637:Clonal Deletion; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D022801:Complementarity Determining Regions; D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta