The kinetic stability of MHC class II:peptide complexes is a key parameter that dictates immunodominance.
T cell priming to exogenous antigens reflects regulated antigen processing in dendritic cells, subsequent homing to lymph nodes, sustained interactions between T cells and antigen-bearing dendritic cells, and, ultimately, selective T cell activation and differentiation. In this study, we test the hypothesis that an intrinsic property of the class II:peptide complex is a key determinant that dictates the specificity of an emerging CD4 T cell response. We found that immunodominant peptides possess extremely long half-lives with class II molecules (t(1/2) > 150 hr), whereas cryptic peptides displayed half-lives of less than 10 hr. Furthermore, and most importantly, by using a peptide shuttle vector and four independent antigens, we demonstrate a direct, causative relationship between the half-life of peptide epitopes and their immunogenicity in vivo. Taken collectively, our results suggest the half-life of class II:peptide complexes is the primary parameter that dictates the ultimate hierarchy of the elicited T cell response.
Lazarski
Christopher A
CA
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, Rochester, New York 14642, USA.
Chaves
Francisco A
FA
Jenks
Scott A
SA
Wu
Shenhong
S
Richards
Katherine A
KA
Weaver
J M
JM
Sant
Andrea J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010455:Peptides