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MHC predictions

5 important questions on MHC predictions

What are the differences between HIV progressors and controllers?

- Progressors
o High copy number
o Causes AIDS
o ART suppressed (antiretroviral therapy)
- Controllers
o Much lower concentration
o No ART required

What is/are the best determint(s) of HIV-1 disease progression?

Rate of HIV disease progression strongly associated with expression of particular HLA-B alleles.

What an how do proteins of HIV-1 virion correlate with the viral load?

Gag responses give a negative correlation  lower viral load
Env responses give a positive correlation  higher viral load

How do we know which peptides bind to an MHC molecule?

Quantitative ELISA:
1. Obtain purified HLA or recombinant heavy chain & β2m
2. Obtain indicator peptide (reporter)
3. Perform dose titration of any inhibitory peptide
4. Separate free from bound peptide
5. Calculate binding and IC50 --> lower IC50, better binding

How do we decide which are good binders and thus epitopes?

Use a fix threshold, and decide that all the
peptides binding better than this threshold are likely epitopes. Take top 1-5% of all possible 9mers as possible epitopes. When comparing peptide binding to different HLA
molecules: fix thresholds do NOT work! Use ranks
instead!