Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules.
The chimpanzee (Pan troglodytes) is an important model for studying the immune response to several human pathogens, but the study of correlates of immunity has been hindered by the fact that little is known about the epitope-binding specificity of chimpanzee (Patr) class I MHC. In the present study we have characterized the peptide binding specificity of several common Patr class I molecules. Using single amino acid substitution analogs and large peptide libraries, quantitative peptide binding motifs have been derived for Patr A*0101, A*0701, A*0901, B*0101, and B*2401. Each molecule was found to bind peptides using position 2 and the C terminus as main anchor contacts. On the other hand, each Patr molecule is associated with a unique binding specificity, and the range of specificities is similar to that seen amongst HLA alleles. A high degree of cross-reactivity was noted between Patr A*0701 and Patr A*0901, suggesting the existence of a Patr-specific supertype. Consistent with previous studies suggesting that some cross-reactivity may exist between HLA and Patr alleles, Patr A*0901 was found to have an appreciable degree of cross-reactivity with molecules of the HLA A24-supertype. Finally, utilizing motif scans and peptide binding and intracellular cytokine staining assays, 77 hepatitis B virus (HBV)-derived epitopes were identified in five chimpanzees that were recently convalescent from acute HBV infection. Because the Patr alleles studied herein were found to be very common in two different chimpanzee populations, the present data should facilitate the use of chimpanzees for immunological studies.
Sidney
John
J
La Jolla Institute for Allergy and Immunology, 3030 Bunker Hill St., Ste. 326, San Diego, CA 92109, USA.
Asabe
Shinichi
S
Peters
Bjoern
B
Purton
Kelly-Anne
KA
Chung
Josan
J
Pencille
Timothy J
TJ
Purcell
Robert
R
Walker
Christopher M
CM
Chisari
Francis V
FV
Sette
Alessandro
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D003429:Cross Reactions; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D006511:Hepatitis B Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D023421:Models, Animal; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000235:genetics / Q000276:immunology*
D015234:HLA-A Antigens; D006511:Hepatitis B Antigens; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D019151:Peptide Library; D010455:Peptides