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Displaying record number 62099

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HXB2 Location	Gag(28-36) p17(28-36) DNA(871..897)	Gag Epitope Map
Author Location	p17(28-36 NL4-3)
Epitope	KYRLKHIVW	Epitope Alignment
		Show epitope variants
Epitope Name	KW9
Species (MHC/HLA)	human(A*24)
Immunogen	computer prediction
Patient MHC/HLA	9213: A*01, A*24, B*38, B*44, C*04
Experimental methods	Other, Relative replication capacity assay
Keywords	vaccine antigen design, viral fitness and reversion

Notes

• Computational models were used to translate published HIV-1 sequence data into quantitative viral fitness landscapes with peaks and valleys, that are a function of the amino acid sequences of its constituent proteins. In this case, Clade B Gag was modeled. Predictions were tested against in vitro fitness measurements and were consistent.
• Epitope KYRLKHIVW is used as an example from Brumme2009 [Brumme et al. PLoS One 4(8):1-12.], where each amino acid position within the epitope is associated with a different energy cost, ΔE, and the greater the cost the higher the fitness penalty. Observed HLA-associated escape position at R30 is the position with the lowest h_i value, i.e. the least energetically costly to change; positions K28 and R30 also have low h_i. In Subject 9213 WT sequence was only found at 79.5% on d1543 along with combinations of other mutation-states prior to that. Infecting strain was the low-energy double-mutant qYRLKHvVW.
• Based on fitness costs, the authors created a rank-ordered bar chart called the "Epitope Index" and marked out immunodominant response associations on it. The epitope index reads Gag: (164-172)-B*57; (162-172)-B*57 i.e. KF11; (167-175)-A*26; (260-267)-B*08; (240-249)-B*57 i.e. TW10; (296-306)-B*14; (147-155)-B*57; (349-359)-A*11; (263-272)-B*27; (269-277)-B*15; (145-155)-A*25; (306-316)-B*44, from highest to lowest fitness costs.
• Brumme2009 is not annotated in this database as epitopes were not immunologically defined, but the table of polymorphisms is available at https://www.hiv.lanl.gov/content/immunology/pdf/2010/escape_article_supplement.html. and a review of the work is available on the main page, hiv.lanl.gov under 'Tools and Data Sets', "Identifying HLA-Associated Polymorphisms in HIV-1" (PDF).

References

Ferguson2013a Andrew L. Ferguson, Jaclyn K. Mann, Saleha Omarjee, Thumbi Ndung'u, Bruce D Walker, and Arup K. Chakraborty. Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design. Immunity, 38(3):606-617, 21 Mar 2013. PubMed ID: 23521886. Show all entries for this paper.