Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1.
The enormous diversity of the T cell pool makes it difficult to determine whether inherent biases in the naive TCR repertoire can influence T cell responsiveness. In C57BL/6 mice the cytotoxic T lymphocyte response to an immunodominant HSV-1 determinant (gB) is characterized by a prominent bias in Vbeta element usage, associated with a conserved and preferentially D element-encoded CDR3 sequence. Comparison of naive and gB-specific T cell populations revealed a similar enrichment of germline D element-encoded CDR3 sequences in the preimmune repertoire. Strikingly, eliminating the germline coding of the gB-specific CDR3 sequence caused an almost complete loss of the dominant subset of gB-specific T cells, illustrating that CDR3 biases can significantly alter both the composition and strength of an immune response.
Wallace
M E
ME
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
Bryden
M
M
Cose
S C
SC
Coles
R M
RM
Schumacher
T N
TN
Brooks
A
A
Carbone
F R
FR
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D022801:Complementarity Determining Regions; D018259:Herpesvirus 1, Human / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D022801:Complementarity Determining Regions; D016056:Immunodominant Epitopes; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell