# The MHC (Major Histocmpatibility Complex) Exceptional Molecules of Birds and Their Relationship to Diseases

## TL;DR

This paper explores unique MHC molecules in passerine birds and their potential links to diseases, highlighting structural differences and gaps in understanding.

## Contribution

The paper identifies unique amino acid residues in passerine MHC class I molecules and discusses their possible implications for disease and immune function.

## Key findings

- Passerine birds have MHC class I molecules with non-canonic amino acid residues at positions 10 and 96.
- MHC class I molecules in passerines may affect interactions with beta-2-microglobulin and immune responses.
- Common bird diseases like malaria and Marek’s disease are potentially linked to MHC, though mechanisms remain unclear.

## Abstract

There are about 5000 species of Passeriformes birds, which are half of the extant ones. Their class I MHC molecules are found to be different from all other studied vertebrates, including other bird species; i.e., amino acid residues 10 and 96 are not the seven canonic residues extant in all other vertebrate molecules. Thus, the canonic residues in MHC class I vertebrate molecules are reduced to five. These differences have physical effects in MHC (Major Histocompatibility Complex) class I alpha chain interaction with beta-2-microglobulin but have yet unknown functional effects. Also, introns show specific Passeriformes distinction both in size and invariance. The studies reviewed in this paper on MHC structure have been done in wild birds that cover most of the world’s passerine habitats. In this context, we are going to expose the most commonly occurring bird diseases with the caveat that MHC and disease linkage pathogenesis is not resolved. In addition, this field is poorly studied in birds; however, common bird diseases like malaria and Marek’s disease are linked to MHC. On the other hand, the main established function of MHC molecules is presenting microbial and other antigens to T cells in order to start immune responses, and they also may modulate the immune system through NK receptors and other receptors (non-classical class I MHC molecules). Also, structural and polymorphic differences between classical class I molecules and non-classical class I molecules are at present not clear, and their definition is blurred. These passerine exceptional MHC class I molecules may influence linkage to diseases, transplantation, and other MHC presentation and self-protection functions. Further studies in more Passeriformes species are ongoing and needed.