DM peptide-editing function leads to immunodominance in CD4 T cell responses in vivo.
DM functions as a peptide editor for MHC class II-bound peptides. We examined the hypothesis that DM peptide editing plays a key role in focusing the in vivo CD4 T cell responses against complex pathogens and protein Ags to only one, or at most a few, immunodominant peptides. Most CD4 T cells elicited in the wild-type BALB/c (H-2d) mice infected with Leishmania major predominantly recognize a single epitope 158-173 within Leishmania homologue of activated receptor for c-kinase (LACK), as is the case when these mice are immunized with rLACK. Using DM-deficient (DM-/-) H-2d mice, we now show that in the absence of DM, the in vivo CD4 T cell responses to rLACK are skewed away from the immunodominant epitopes and are diversified to include two novel epitopes (LACK 33-48 and 261-276). DM-/- B10.BR (H-2k) mice showed similar results. These results constitute the first demonstration of the role of DM peptide editing in sculpting the specificity and immunodominance in in vivo CD4 T cell responses.
Nanda
Navreet K
NK
Departments of Microbiology and Immunology, and Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington DC 20057, USA. nkn3@georgetown.edu
Bikoff
Elizabeth K
EK
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000469:parasitology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000235:genetics; D018320:Leishmania major / Q000235:genetics / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology
D000953:Antigens, Protozoan; C416189:H2-M antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania