Direct link between mhc polymorphism, T cell avidity, and diversity in immune defense.
Major histocompatibility complex (mhc)-encoded molecules govern immune responses by presenting antigenic peptides to T cells. The extensive polymorphism of genes encoding these molecules is believed to enhance immune defense by broadening the array of antigenic peptides available for T cell recognition, but direct evidence supporting the importance of this mechanism in combating pathogens is limited. Here we link mhc polymorphism-driven diversification of the cytotoxic T lymphocyte (CTL) repertoire to the generation of high-avidity, protective antiviral T cells and to superior antiviral defense. Thus, much of the beneficial effect of the mhc polymorphism in immune defense may be due to its critical influence on the properties of the selected CTL repertoire.
Messaoudi
Ilhem
I
Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
Guevara Patiño
Jose A
JA
Dyall
Ruben
R
LeMaoult
Joël
J
Nikolich-Zugich
Janko
J
D019264:Adoptive Transfer; D000818:Animals; D022801:Complementarity Determining Regions; D003602:Cytotoxicity, Immunologic; D005260:Female; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D022801:Complementarity Determining Regions; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta