Dear Veronika,

Major Histocompatibility Complex (MHC) molecules play crucial roles in the immune system by presenting antigens to T cells, thereby initiating immune responses against pathogens and foreign substances. There are two main classes of MHC molecules: MHC class I and MHC class II.

MHC Class I:

• Function: Present endogenous antigens (from inside the cell) to CD8+ cytotoxic T cells.
• Structure: Composed of a heavy chain (encoded by genes like HLA-A, HLA-B, HLA-C) and a light chain (β2-microglobulin).
• Genetic Variability: MHC class I alleles are highly polymorphic, meaning they have many different forms (alleles) in the human population. This diversity allows them to present a wide range of antigens.

MHC Class II:

• Function: Present exogenous antigens (from outside the cell, typically ingested or phagocytosed) to CD4+ helper T cells.
• Structure: Composed of two chains (α and β chains, encoded by genes like HLA-DP, HLA-DQ, HLA-DR).
• Genetic Variability: MHC class II alleles are also highly polymorphic, contributing to the ability of the immune system to recognize and respond to a diverse array of pathogens.

Copy Number Variations (CNVs) and Unassigned Loci:

Analysis:

• Genotyping and Sequencing: To study MHC alleles with CNVs and unassigned loci, researchers typically use advanced genotyping and sequencing techniques.
• Impact on Immune Responses: Understanding the diversity (allelic variation and CNVs) within MHC genes is crucial for studying how different individuals respond to infections, vaccines, and autoimmune diseases.
• Clinical Relevance: MHC alleles with specific CNVs or mutations may predispose individuals to certain diseases or affect their responses to therapies.
• Challenges: Analyzing MHC alleles with CNVs and unassigned loci can be challenging due to the high complexity and polymorphism of the MHC region, requiring sophisticated bioinformatics tools and large-scale genomic data.

In summary, MHC class I and II alleles exhibit high diversity due to polymorphisms, and their study includes understanding CNVs and exploring unassigned loci within the MHC region, which are crucial for comprehending immune responses and disease susceptibilities.

Thanks & Regards,

Lenin Kumar B.