BACKGROUND: Polymorphism among class I molecules of the major histocompatibility complex (MHC) confers allotypic specificity on the peptides that these molecules bind and present to cytotoxic T lymphocytes. Evolution of new human HLA class I alleles usually involves gene recombination events that replace a segment of one allele with the homologous region of another. In this study, the impact of these evolutionary changes has been assessed by comparison of the peptide-binding specificities of six related HLA-B allotypes. RESULTS: Endogenous peptides bound by HLA-B*5401, HLA-B*5501, HLA-B*5502, HLA-B*5601, HLA-B*6701 and HLA-B*0702 were characterized. Despite differing by 1-9 of the amino-acid residues comprising their peptide-binding sites, all these allotypes share a dominant preference for peptides that have proline at position 2. Polymorphism results in differing selection of carboxy-terminal and secondary anchor residues, but the peptide-binding specificities are sufficiently similar that there is overlap in the repertoires of peptides bound by these allotypes. Complete sequence determination of individual peptides revealed four that could be isolated from two or more allotypes. Members of the closely related HLA-B22 family--HLA-B*5401, HLA-B*5501, HLA-B*5502 and HLA-B*5601--show only minor differences in their peptide-binding specificities. This marked similarity is reflected at the functional level, as alloreactive cytotoxic T lymphocytes generated against HLA-B*5401 and HLA-B*5501 exhibited cross-reactive recognition. CONCLUSION: The isolation of identical endogenously bound peptides from six HLA-B allotypes demonstrates overlap in the repertoires of peptides bound in vivo by different allotypes. We speculate that the shared preference for binding peptides with proline at position 2 reflects a selective pressure to retain this specificity, which may be based upon peptide availability in vivo. Characterization of the overlap between the repertoires of peptides bound by HLA-B allotypes could simplify the development of peptide-based vaccines that are targeted to cytotoxic T cells, as single peptides would be effective for humans of different HLA types.
BACKGROUND: Polymorphism among class I molecules of the major histocompatibility complex (MHC) confers allotypic specificity on the peptides that these molecules bind and present to cytotoxic T lymphocytes. Evolution of new human HLA class I alleles usually involves gene recombination events that replace a segment of one allele with the homologous region of another. In this study, the impact of these evolutionary changes has been assessed by comparison of the peptide-binding specificities of six related HLA-B allotypes. RESULTS: Endogenous peptides bound by HLA-B*5401, HLA-B*5501, HLA-B*5502, HLA-B*5601, HLA-B*6701 and HLA-B*0702 were characterized. Despite differing by 1-9 of the amino-acid residues comprising their peptide-binding sites, all these allotypes share a dominant preference for peptides that have proline at position 2. Polymorphism results in differing selection of carboxy-terminal and secondary anchor residues, but the peptide-binding specificities are sufficiently similar that there is overlap in the repertoires of peptides bound by these allotypes. Complete sequence determination of individual peptides revealed four that could be isolated from two or more allotypes. Members of the closely related HLA-B22 family--HLA-B*5401, HLA-B*5501, HLA-B*5502 and HLA-B*5601--show only minor differences in their peptide-binding specificities. This marked similarity is reflected at the functional level, as alloreactive cytotoxic T lymphocytes generated against HLA-B*5401 and HLA-B*5501 exhibited cross-reactive recognition. CONCLUSION: The isolation of identical endogenously bound peptides from six HLA-B allotypes demonstrates overlap in the repertoires of peptides bound in vivo by different allotypes. We speculate that the shared preference for binding peptides with proline at position 2 reflects a selective pressure to retain this specificity, which may be based upon peptide availability in vivo. Characterization of the overlap between the repertoires of peptides bound by HLA-B allotypes could simplify the development of peptide-based vaccines that are targeted to cytotoxic T cells, as single peptides would be effective for humans of different HLA types.
Authors: Thorsten U Vogel; Thomas C Friedrich; David H O'Connor; William Rehrauer; Elizabeth J Dodds; Heather Hickman; William Hildebrand; John Sidney; Alessandro Sette; Austin Hughes; Helen Horton; Kathy Vielhuber; Richard Rudersdorf; Ivna P De Souza; Matthew R Reynolds; Todd M Allen; Nancy Wilson; David I Watkins Journal: J Virol Date: 2002-11 Impact factor: 5.103
Authors: Nicole Frahm; Karina Yusim; Todd J Suscovich; Sharon Adams; John Sidney; Peter Hraber; Hannah S Hewitt; Caitlyn H Linde; Daniel G Kavanagh; Tonia Woodberry; Leah M Henry; Kellie Faircloth; Jennifer Listgarten; Carl Kadie; Nebojsa Jojic; Kaori Sango; Nancy V Brown; Eunice Pae; M Tauheed Zaman; Florian Bihl; Ashok Khatri; Mina John; Simon Mallal; Francesco M Marincola; Bruce D Walker; Alessandro Sette; David Heckerman; Bette T Korber; Christian Brander Journal: Eur J Immunol Date: 2007-09 Impact factor: 5.532
Authors: Aleksandr Lazaryan; Tao Wang; Stephen R Spellman; Hai-Lin Wang; Joseph Pidala; Taiga Nishihori; Medhat Askar; Richard Olsson; Machteld Oudshoorn; Hisham Abdel-Azim; Agnes Yong; Manish Gandhi; Christopher Dandoy; Bipin Savani; Gregory Hale; Kristin Page; Menachem Bitan; Ran Reshef; William Drobyski; Steven Ge Marsh; Kirk Schultz; Carlheinz R Müller; Marcelo A Fernandez-Viña; Michael R Verneris; Mary M Horowitz; Mukta Arora; Daniel J Weisdorf; Stephanie J Lee Journal: Haematologica Date: 2016-05-31 Impact factor: 9.941
Authors: Mehdi Tafti; Gert J Lammers; Yves Dauvilliers; Sebastiaan Overeem; Geert Mayer; Jacek Nowak; Corinne Pfister; Valérie Dubois; Jean-François Eliaou; Hans-Peter Eberhard; Roland Liblau; Aleksandra Wierzbicka; Peter Geisler; Claudio L Bassetti; Johannes Mathis; Michel Lecendreux; Ramin Khatami; Raphaël Heinzer; José Haba-Rubio; Eva Feketeova; Christian R Baumann; Zoltán Kutalik; Jean-Marie Tiercy Journal: Sleep Date: 2016-03-01 Impact factor: 5.849
Authors: G K Balendiran; J C Solheim; A C Young; T H Hansen; S G Nathenson; J C Sacchettini Journal: Proc Natl Acad Sci U S A Date: 1997-06-24 Impact factor: 11.205
Authors: Christian B Willberg; Keith E Garrison; R Brad Jones; Duncan A Meiklejohn; Gerald Spotts; Teri J Liegler; Mario A Ostrowski; Annika C Karlsson; Frederick M Hecht; Douglas F Nixon Journal: PLoS One Date: 2010-04-21 Impact factor: 3.240