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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.

Type

Journal article

Journal

J Immunol

Publication Date

15/11/2005

Volume

175

Pages

6473 - 6480

Keywords

Amino Acid Sequence, Animals, Antigen-Presenting Cells, Antigens, Protozoan, CD4-Positive T-Lymphocytes, Female, Histocompatibility Antigens Class II, Immunization, Immunodominant Epitopes, Leishmania major, Leishmaniasis, Cutaneous, Mice, Mice, Inbred BALB C, Mice, Knockout, Molecular Sequence Data, Protozoan Proteins