Complementary DNA sequence of the novel HLA-B*3704 allele

Area of Science:

• Immunogenetics
• Molecular Biology
• Human Leukocyte Antigen (HLA) research

Background:

• The Human Leukocyte Antigen (HLA) system plays a crucial role in immune response and transplantation.
• Genetic variations within HLA loci can lead to diverse serological phenotypes and influence immune system function.
• Ambiguous HLA typing results necessitate detailed molecular characterization to identify novel alleles.

Purpose of the Study:

• To identify and characterize a novel HLA-B allele detected through ambiguous serological typing.
• To elucidate the molecular basis of the observed phenotypic differences between the novel and known HLA-B alleles.
• To understand the potential functional implications of the identified genetic variations on antigen presentation.

Main Methods:

• Polymerase chain reaction with sequence-specific oligonucleotides (PCR-SSO) for initial allele identification.
• Reverse transcription-polymerase chain reaction (RT-PCR) amplification of the coding region.
• Molecular cloning and nucleotide sequencing for complete genetic analysis.

Main Results:

• Identification of a novel HLA-B allele, designated HLA-B*3704, in a Spanish Caucasoid individual.
• Comparison with HLA-B*3701 revealed a single nucleotide difference leading to a His171Tyr substitution.
• The substitution occurs in the alpha-helix of the alpha-2 domain, within the peptide-binding site's A pocket.

Conclusions:

• The novel HLA-B*3704 allele has been molecularly defined.
• The His171Tyr substitution is proposed to alter the antigen-presenting capabilities of HLA-B*3704.
• This substitution likely accounts for the distinct serological phenotype observed for HLA-B*3704 compared to HLA-B*3701.