Polymorphic analysis of the three MHC-linked HSP70 genes

Area of Science:

• Immunogenetics
• Molecular Biology
• Protein Science

Background:

• The human major histocompatibility complex (MHC) class III region contains three heat shock protein 70 (HSP70) genes.
• HSP70 proteins are crucial for cellular stress response and protein folding.

Purpose of the Study:

• To investigate the polymorphism of three HSP70 genes (HSP70-1, HSP70-2, and HSP70-Hom) within the human MHC class III region.
• To determine if sequence variations in these genes correlate with amino acid changes and functional differences.

Main Methods:

• Specific amplification of the three HSP70 genes from genomic DNA of various human haplotypes.
• Nucleotide sequencing of the amplified HSP70 genes.
• Comparative analysis of nucleotide sequences to identify variations.

Main Results:

• HSP70-1 and HSP70-2 genes, encoding major heat-inducible HSP70, exhibited minimal nucleotide sequence variation, with no associated amino acid polymorphism.
• The HSP70-Hom gene, encoding a non-heat-inducible but related protein, displayed a consistent Met to Thr amino acid substitution at residue 493 in several tested haplotypes.
• This polymorphic residue is located within the predicted peptide-binding site of the HSP70-Hom protein.

Conclusions:

• The major heat-inducible HSP70 genes (HSP70-1, HSP70-2) in the human MHC class III region are highly conserved at the nucleotide and amino acid levels.
• HSP70-Hom exhibits a specific amino acid polymorphism within its peptide-binding site, suggesting potential functional implications for this non-heat-inducible HSP70 family member.