Ask a Scientist:
How Do I Decode the HLA System?

ask a scientist

ask a scientistDespite being central to adaptive immunity and transplantation, the genetic locus that encodes Human Leukocyte Antigens (HLA) can be confusing to scientists who don’t specialize in it.

HLA Background

The molecules that belong to the HLA system were first defined using antibodies: the class I antigens (A, B and C) and the class II antigen (D). At first, these D antigens seemed to be related to antigens that triggered transplant rejection, and were labeled DR for “D Related.” But the confusion was just beginning.

Advancements in molecular genetic methods revealed far more differences between individuals than could be appreciated using antibodies. As more people were genetically typed for HLA, more HLA alleles were discovered. Today, there are over 2,000 different alleles described for each of these genes.

Today’s HLA Nomenclature

To further confuse non-specialists, the HLA nomenclature has changed several times over the years. For example, HLA-A2.1 is now HLA-A*0201, and HLA-DR2 is now HLA-DRB1*15 or HLA-DRB1*16.

The current nomenclature assigns at least four digits to each allele. You will notice many of the alleles we list have only two digits. These two digits define a type that consists of closely related groups of alleles. Some types have one specific allele that is much more frequent than others in the human population. For example, HLA-A*02 is expressed by 50% of Caucasians, so it is frequently studied. When a person of European descent has the HLA-A*02 type, 97% of the time it is specifically the A*02:01 allele.

Other types are not dominated by a single allele. The HLA-DRB1*04 type has a good chance of being DRB1*04:01 or DRB1*04:04 in European Caucasians, but is more likely to be DRB1*04:05 if the donor is Japanese.

We created a convenient guide to decode HLA typing, provide a glossary of popular terms, and help you quickly identify the information you’re looking for.

Quick Guide to Understanding HLA Typing Nomenclature

HLA Typing Nomenclature, How to Understand the HLA System

Locus – The gene the allele is a modification of. See table below for examples.

Allele Group – The allele’s antigen type, typically found via serotyping. Antigens with the same allele group number will not react with one another.

HLA Protein – The protein for which the allele codes.

Synonymous Mutation within Coding Region – Identifies an allele variant with a different DNA sequence that produces the same protein.

Mutation Outside Coding Region – Identifies a nucleotide polymorphism outside of the gene’s coding region.

Expression Level – Denotes a change in expression. Can be one of six letters:

  • N – Null allele
  • L – Lower than normal cell surface expression
  • S – Soluble protein not found on cell surface
  • Q – Questionable
  • C – Protein present in cytoplasm but not cell surface
  • A – Aberrant expression

Most Important HLA Genes

Most Important HLA Genes

Where Can I Find HLA Typing Information?

HLA typing information can usually be found on any Certificate of Analysis under the donor profile. Understanding the HLA type is vital to the outcomes of your experiments. If the HLA information is not on the Certificate of Analysis, or if you cannot readily find the Certificate of Analysis for the cells you buy, always ask your supplier.

As part of a comprehensive donor profile, all Astarte cell products include a Certificates of Analysis with HLA typing for HLA-A, HLA-B, HLA-C, and HLA-DRB1. Additional HLA typing is available upon request.

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