We get many orders and requests for donors who are HLA-A*0201 positive and CMV positive, and for good reason. Scientists know that the HLA-A*0201 allele is the most common allele found in the European/North American Caucasian population, expressed by about half of all individuals. But are there alternatives to HLA-A*0201 positive donors? And should you be testing other alleles in your experiments?
Let’s start by looking closer at the HLA-A*0201 allele.
Why HLA-A*0201 is So Popular
There are many reasons scientists focus on the HLA-A*0201 allele, a few of which are described below.
- The T cell immune response is dependent on peptide binding to HLA molecules, so researchers often study the interaction of these molecules with various antigens. With thousands of HLA molecules to choose from, it makes sense to study the most commonly expressed allele for maximum relevance.
- The peptide binding motif for HLA-A*0201 is well understood.
- HLA multimers are readily available for staining antigen specific T cells.
- There are even mice that express the HLA-A*0201 allele, making it possible to do pre-clinical testing in a biological system closer to humans.
Alternatives to HLA-A*0201
Because only half of the European/North American Caucasian population is HLA-A*0201 positive, the other half of that population is HLA-A*0201 negative. Exclusive use of HLA-A*0201 positive donors can limit the application of your findings.
Some of the tools used to study HLA-A*0201 alleles—such as binding peptides and HLA multimer reagents—have been developed for other HLA alleles commonly expressed in the U.S. Caucasian population:
- HLA-A*01:01 (about 30%)
- HLA-A*03:01 (about 26–28%)
- HLA-B*07:02 (about 26%)
- HLA-B*35 (about 10–15%)
While peptide epitopes—the amino acids to which a T cell receptor binds—have not yet been defined for every antigen of interest, many have been. The Immune Epitope Database is a great resource for this subject.
Why Consider the Alternatives?
Including other HLA alleles in your studies extends the relevance of your data to more individuals and increases the pool of donors available to you. These alternative HLA alleles are often more abundant and readily available than HLA-A*0201 alleles due to the high demand and competition for PBMC from HLA-A*0201 positive donors.
We have a variety of donors who are HLA-B*35 and CMV positive, making them great replacements for HLA-A*0201 donors. There is also a known epitope for the HLA-B*35 allele. We have prepared a CMV specific T cell line from an HLA-B*35 positive donor that recognizes peptide at low concentrations.
While you shouldn’t stop studying HLA-A*0201 positive donors altogether, you may want to consider expanding your studies to include some of these alternatives.