The MHC class I-restricted T cell response to Sendai virus infection in C57BL/6 mice: a single immunodominant epitope elicits an extremely diverse repertoire of T cells.
We have used Sendai virus infection of C57BL/6 mice as a model with which to study the T cell response to a single MHC class I epitope. Cells taken from the bronchoalveolar lavage or restimulated in vitro from the mediastinal lymph nodes of virus-infected mice were strongly cytotoxic for a single nucleoprotein epitope, NP324-332/Kb. To correlate TCR usage with specificity for the immunodominant epitope, we generated T cell hybridomas from the bronchoalveolar lavage and mediastinal lymph node cells of C57BL/6 mice at the peak of infection. Altogether, 20 hybridomas were identified that specifically secreted IL-2 in response to NP324-332-pulsed L929-Kb cells. TCR usage in this panel of hybridomas was extremely diverse. Over half of the available J beta and V beta elements present in the C57BL/6 strain of mouse were represented in the hybridomas. Similarly, V alpha usage was also diverse and all 12 of the alpha chains sequenced used distinct J alpha elements. The only relatively conserved feature of the TCR in these hybridomas was the presence of an arginine residue in the junctions of 70% of the beta chains. These data demonstrate that a diverse repertoire of TCR is able to recognize a single MHC class I epitope. Moreover, the data demonstrate that mice make use of this potential diversity in the primary response to a natural viral infection.
Cole
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GA
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105.
Hogg
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TL
Woodland
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000235:genetics; D006825:Hybridomas / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D010446:Peptide Fragments