T Cell receptor clonotype influences epitope hierarchy in the CD8+ T cell response to respiratory syncytial virus infection.
CD8+ T cell responses are important for recognizing and resolving viral infections. To better understand the selection and hierarchy of virus-specific T cell responses, we compared the T cell receptor (TCR) clonotype in parent and hybrid strains of respiratory syncytial virus-infected mice. K(d)M2(82-90) (SYIGSINNI) in BALB/c and D(b)M(187-195) (NAITNAKII) in C57Bl/6 are both dominant epitopes in parent strains but assume a distinct hierarchy, with K(d)M2(82-90) dominant to D(b)M(187-195) in hybrid CB6F1/J mice. The dominant K(d)M2(82-90) response is relatively public and is restricted primarily to the highly prevalent Vβ13.2 in BALB/c and hybrid mice, whereas D(b)M(187-195) responses in C57BL/6 mice are relatively private and involve multiple Vβ subtypes, some of which are lost in hybrids. A significant frequency of TCR CDR3 sequences in the D(b)M(187-195) response have a distinct "(D/E)WG" motif formed by a limited number of recombination strategies. Modeling of the dominant epitope suggested a flat, featureless structure, but D(b)M(187-195) showed a distinctive structure formed by Lys(7). The data suggest that common recombination events in prevalent Vβ genes may provide a numerical advantage in the T cell response and that distinct epitope structures may impose more limited options for successful TCR selection. Defining how epitope structure is interpreted to inform T cell function will improve the design of future gene-based vaccines.
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, Maryland 20892-3017, USA.
Padma
P
Billam
Kathryn L
KL
Bonaparte
Jie
J
Liu
Tracy J
TJ
Ruckwardt
Man
M
Chen
Alex B
AB
Ryder
Rui
R
Wang
Pradyot
P
Dash
Paul G
PG
Thomas
Barney S
BS
Graham
D020816:Amino Acid Motifs; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002678:Chimera / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013045:Species Specificity
D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D016693:Receptors, Antigen, T-Cell, alpha-beta