HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Colombetti, S. Articles by Lévy, F. Search for Related Content PubMed PubMed Citation Articles by Colombetti, S. Articles by Lévy, F. Pubmed/NCBI databases Substance via MeSH

Impact of Orthologous Melan-A Peptide Immunizations on the Anti-Self Melan-A/HLA-A2 T Cell Cross-Reactivity¹

Sara Colombetti^*, Theres Fagerberg^*,, Petra Baumgärtner, Laurence Chapatte^*, Daniel E. Speiser^,¶, Nathalie Rufer^,¶, Olivier Michielin^*,,|| and Frédéric Lévy^2,*,¶

^* Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; Swiss Institute for Bioinformatics, Lausanne, Switzerland; Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland; Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland; ^¶ National Center of Competence in Research Molecular Oncology, Epalinges, Switzerland; and ^|| Multidisciplinary Oncology Center, Lausanne, Switzerland

In HLA-A2 individuals, the CD8 T cell response against the differentiation Ag Melan-A is mainly directed toward the peptide Melan-A_26–35. The murine Melan-A_24–33 sequence encodes a peptide that is identical with the human Melan-A_26–35 decamer, except for a Thr-to-Ile substitution at the penultimate position. Here, we show that the murine Melan-A_24–33 is naturally processed and presented by HLA-A2 molecules. Based on these findings, we compared the CD8 T cell response to human and murine Melan-A peptide by immunizing HLA-A2 transgenic mice. Even though the magnitude of the CTL response elicited by the murine Melan-A peptide was lower than the one elicited by the human Melan-A peptide, both populations of CTL recognized the corresponding immunizing peptide with the same functional avidity. Interestingly, CTL specific for the murine Melan-A peptide were completely cross-reactive against the orthologous human peptide, whereas anti-human Melan-A CTL recognized the murine Melan-A peptide with lower avidity. Structurally, this discrepancy could be explained by the fact that Ile³² of murine Melan-A_24–33 created a larger TCR contact area than Thr³⁴ of human Melan-A_26–35. These data indicate that, even if immunizations with orthologous peptides can induce strong specific T cell responses, the quality of this response against syngeneic targets might be suboptimal due to the structure of the peptide-TCR contact surface.