HLA & Immunogenomics Analysis

Pipeline for exploring HLA gene families, MHC-peptide binding, epitope associations, and their clinical implications in transplantation, vaccine development, and cancer immunotherapy. Bridges immunogenetic databases (IMGT, IEDB) with functional annotation (UniProt) and druggability data (DGIdb).

Reasoning Strategy

HLA analysis is fundamentally about peptide presentation: the polymorphism of HLA molecules determines which peptides are displayed to T cells, which in turn governs disease susceptibility, transplant rejection, drug hypersensitivity, and vaccine immunogenicity. HLA type affects disease susceptibility for autoimmune conditions (HLA-B27 and ankylosing spondylitis), transplant rejection (HLA mismatch drives alloresponse), drug hypersensitivity (abacavir causes severe hypersensitivity reactions only in HLA-B*57:01 carriers), and vaccine design (epitopes must be presented by the recipient's HLA alleles to elicit a T-cell response). Class I and Class II HLA molecules have fundamentally different binding grooves, peptide lengths, and T-cell partners — never conflate them. The absence of an epitope from IEDB means it has not been tested, not that it cannot bind.

LOOK UP DON'T GUESS: Never assume an allele's binding properties or population frequency — query IEDB for experimental binding data and IMGT for allele annotation. Do not guess which HLA alleles are common in a population; look up published frequency data via PubMed.

Guiding principles:

1. HLA nomenclature precision -- HLA allele names follow strict conventions (e.g., HLA-A*02:01); get the resolution level right
2. MHC class awareness -- Class I (A, B, C) and Class II (DR, DQ, DP) have different binding properties and clinical roles
3. Species context -- most queries target human HLA, but MHC exists across vertebrates; confirm species early
4. Evidence layering -- combine binding data (IEDB) with gene annotation (IMGT) and structural context (UniProt)
5. Clinical translation -- connect molecular findings to transplant matching, vaccine targets, or immunotherapy response
6. English-first queries -- use English terms in all tool calls; respond in the user's language