Crystal Structures of HLA-A*0201 Complexed with Melan-A/MART-1[subscript 26(27L)-35] Peptidomimetics Reveal Conformational Heterogeneity and Highlight Degeneracy of T Cell Recognition

Journal Article · Thu Oct 07 00:00:00 EDT 2010 · J. Med. Chem.

DOI:https://doi.org/10.1021/jm100683p· OSTI ID:1002785

Douat-Casassus, Celine; Borbulevych, Oleg; Tarbe, Marion; Gervois, Nadine; Jotereau, Francine; Baker, Brian M; Quideau, Stphane ^[1]

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1. CNRS-UMR

There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrate that antigenic peptidomimetics of the Melan-A/MART-1{sub 26(27L)-35} melanoma antigen adopt strikingly different conformations when bound to MHC-I, highlighting the degeneracy of T cell recognition and revealing the challenges associated with mimicking native peptide conformation.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1002785
• Journal Information: J. Med. Chem., Vol. 53, Issue (19) ; 10, 2010; ISSN 0022-2623
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ANTIGENS
CRYSTAL STRUCTURE
ENGINEERS
HISTOCOMPATIBILITY COMPLEX
MELANOMAS
NEOPLASMS
PEPTIDES
PROTEINS
VACCINES