title: Characterization of the peptide binding specificity of the HLA class I alleles B*38:01 and B*39:06.
abstract: B*38:01 and B*39:06 are present with phenotypic frequencies <2% in the general population, but are of interest as B*39:06 is the B allele most associated with type 1 diabetes susceptibility and 38:01 is most protective. A previous study derived putative main anchor motifs for both alleles based on peptide elution data. The present study has utilized panels of single amino acid substitution peptide libraries to derive detailed quantitative motifs accounting for both primary and secondary influences on peptide binding. From these analyses, both alleles were confirmed to utilize the canonical position 2/C-terminus main anchor spacing. B*38:01 preferentially bound peptides with the positively charged or polar residues H, R, and Q in position 2 and the large hydrophobic residues I, F, L, W, and M at the C-terminus. B*39:06 had a similar preference for R in position 2, but also well-tolerated M, Q, and K. A more dramatic contrast between the two alleles was noted at the C-terminus, where the specificity of B*39:06 was clearly for small residues, with A as most preferred, followed by G, V, S, T, and I. Detailed position-by-position and residue-by-residue coefficient values were generated from the panels to provide detailed quantitative B*38:01 and B*39:06 motifs. It is hoped that these detailed motifs will facilitate the identification of T cell epitopes recognized in the context of two class I alleles associated with dramatically different dispositions towards type 1 diabetes, offering potential avenues for the investigation of the role of CD8 T cells in this disease.
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schloss
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Moore
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Lindvall
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, VA, 222904, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Wriston
authors.affiliation: Departments of Chemistry and Pathology, University of Virginia, Charlottesville, VA, 222904, USA.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, VA, 222904, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.|Department of Medicine (Division of Endocrinology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
authors.forename: Teresa P
authors.initials: TP
authors.lastname: DiLorenzo
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA. alex@liai.org.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D000595:Amino Acid Sequence; D059945:HLA-B38 Antigen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D059946:HLA-B39 Antigen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D059945:HLA-B38 Antigen; D059946:HLA-B39 Antigen; D010455:Peptides
keywords: Antigen presentation; Epitopes; Major histocompatibility complex; Type 1 diabetes