Class II MHC self-antigen presentation in human B and T lymphocytes.
Human CD4(+) T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4(+) T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.
Program in Immunology, Harvard Medical School, Boston, Massachusetts, United States of America.
Cristina Maria
CM
Costantino
Eric
E
Spooner
Hidde L
HL
Ploegh
David A
DA
Hafler
D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000302:isolation & purification; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification; D020543:Proteome / Q000032:analysis / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D000936:Antigen-Antibody Complex; D001324:Autoantigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D020543:Proteome