title: Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude.
abstract: Cell-mediated immunity stems from the proliferation of naive T lymphocytes expressing T cell antigen receptors (TCRs) specific for foreign peptides bound to host major histocompatibility complex (MHC) molecules. Because of the tremendous diversity of the T cell repertoire, naive T cells specific for any one peptide:MHC complex (pMHC) are extremely rare. Thus, it is not known how many naive T cells of any given pMHC specificity exist in the body or how that number influences the immune response. By using soluble pMHC class II (pMHCII) tetramers and magnetic bead enrichment, we found that three different pMHCII-specific naive CD4(+) T cell populations vary in frequency from 20 to 200 cells per mouse. Moreover, naive population size predicted the size and TCR diversity of the primary CD4(+) T cell response after immunization with relevant peptide. Thus, variation in naive T cell frequencies can explain why some peptides are stronger immunogens than others.
authors: Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors: James J
authors: JJ
authors: Moon
authors: H Hamlet
authors: HH
authors: Chu
authors: Marion
authors: M
authors: Pepper
authors: Stephen J
authors: SJ
authors: McSorley
authors: Stephen C
authors: SC
authors: Jameson
authors: Ross M
authors: RM
authors: Kedl
authors: Marc K
authors: MK
authors: Jenkins
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D014644:Genetic Variation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008817:Mice, Mutant Strains; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell
references: J Immunol. 2000 Jan 15;164(2):986-93
references: 10623848
references: J Immunol. 2000 Jun 1;164(11):5782-7
references: 10820256
references: J Immunol. 2000 Dec 15;165(12):6833-9
references: 11120806
references: Immunity. 2000 Dec;13(6):771-82
references: 11163193
references: Annu Rev Immunol. 2001;19:23-45
references: 11244029
references: Nat Immunol. 2001 May;2(5):415-22
references: 11323695
references: Nat Immunol. 2001 May;2(5):423-9
references: 11323696
references: Nat Med. 2001 Aug;7(8):913-9
references: 11479623
references: J Exp Med. 2002 Mar 4;195(5):657-64
references: 11877489
references: Immunity. 2002 Mar;16(3):365-77
references: 11911822
references: Microbes Infect. 2002 Apr;4(5):531-7
references: 11959508
references: Immunity. 2002 Aug;17(2):191-200
references: 12196290
references: Annu Rev Immunol. 2006;24:419-66
references: 16551255
references: Science. 2006 Apr 7;312(5770):114-6
references: 16513943
references: Immunol Rev. 2006 Jun;211:39-48
references: 16824115
references: Immunity. 2006 Aug;25(2):261-70
references: 16879996
references: Immunity. 2006 Oct;25(4):533-43
references: 17046682
references: J Immunol. 2006 Nov 15;177(10):6705-12
references: 17082583
references: J Virol. 2007 Feb;81(4):2002-11
references: 17151096
references: J Exp Med. 2007 Feb 19;204(2):299-309
references: 17261633
references: Nat Immunol. 2007 Apr;8(4):388-97
references: 17322886
references: Immunity. 2007 Jun;26(6):827-41
references: 17555991
references: J Exp Med. 2004 Feb 16;199(4):559-65
references: 14769854
references: Nat Immunol. 2004 Apr;5(4):418-25
references: 14991052
references: J Immunol. 2004 Aug 15;173(4):2494-9
references: 15294964
references: J Exp Med. 1972 Aug 1;136(2):241-60
references: 4114497
references: J Immunol. 1984 Oct;133(4):2067-74
references: 6332146
references: Genome. 1989;31(2):652-5
references: 2632348
references: Nature. 1991 Oct 17;353(6345):660-2
references: 1656278
references: Cell. 1994 Jan 14;76(1):17-27
references: 8287475
references: Nature. 1994 May 12;369(6476):151-4
references: 8177320
references: Science. 1995 Apr 7;268(5207):106-11
references: 7535476
references: Immunity. 1995 Jun;2(6):655-63
references: 7540944
references: J Exp Med. 1996 May 1;183(5):2087-95
references: 8642319
references: Immunity. 1998 Feb;8(2):167-75
references: 9491998
references: Immunity. 1998 Mar;8(3):353-62
references: 9529152
references: Immunol Cell Biol. 1998 Feb;76(1):34-40
references: 9553774
references: Annu Rev Immunol. 1998;16:201-23
references: 9597129
references: Immunity. 1998 Aug;9(2):169-78
references: 9729037
references: Protein Sci. 1999 Apr;8(4):921-9
references: 10211839
references: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9781-6
references: 10449771
references: Immunity. 2004 Nov;21(5):669-79
references: 15539153
references: J Exp Med. 2005 May 16;201(10):1555-65
references: 15897273
references: Nat Immunol. 2005 Aug;6(8):793-9
references: 16025119
references: J Immunol. 2006 Mar 1;176(5):3028-36
references: 16493061
references: J Immunol. 2006 Mar 1;176(5):3037-43
references: 16493062