A Practical MHC/HLA Primer for Neoantigen and Vaccine Work

July 11, 2026 7 min read

Immunogenetics Neoantigen Bioinformatics

If you work on neoantigen discovery, vaccine design, or transplant-adjacent analysis, MHC/HLA literacy pays for itself quickly. Here is the compact mental model I keep coming back to.

Class I vs Class II (the working distinction)

Class I presents endogenous peptides to CD8 T cells
Class II presents exogenous peptides to CD4 T cells

Everything else — allele naming, typing accuracy, binder prediction — sits on top of that split.

Tooling I mention often

IPD-IMGT/HLA — allele reference
OptiType / HLA-HD — typing from sequencing data
NetMHCpan — peptide–MHC binding prediction
IEDB — epitope resources and analysis utilities

              Practical tip: separate “typing confidence,” “peptide generation,” and “presentation/binding prediction” as three stages.
              Mixing them into one black box makes failures hard to debug.
            

Where this shows up

Transplant matching
Neoantigen ranking for personalized immunotherapy
Vaccine epitope selection

This is an expanded version of a short HLA refresher I posted on X — meant as a checklist, not a textbook.

Expanded from notes I shared on X. For more writing, see the blog index.