Do you have a pesky little habit you just can’t kick? One that’s hard to ignore because you’re reminded of it everywhere you turn? Your friends are doing it, your colleagues are doing it, even your parents are doing it! (If they are research scientists.) 

We are, of course, talking about the habit of focusing exclusively on the HLA-A*02:01 allele. What did you think?
HLA-A*02:01 is the most studied allele, and for good reason. It’s the most common allele found in the Caucasian population, making it readily available to researchers and relevant to a large portion of the population.

Focusing exclusively on HLA-A*02:01 in your studies can limit the applicability of your research and findings. Let’s make a pact to kick the habit in 2020.  

A Way-Too-Early New Year’s Resolution: Expand Your Research Horizons

There are many other A alleles and B alleles that can present antigens. Let’s take one B allele as an example: HLA-B*35. 

The HLA-B*35 allele is found in more than 10% of the Caucasian population in the United States and is also frequently found in Native American and African American populations. Studying alleles like HLA-B*35 can give us insights applicable to large groups of people, open doors to understanding immune responses across populations, and eventually lead to treatments and cures that can save more lives.

EthnicityPercentage of Individuals Who Express HLA-B*35
African-American13%
European Caucasian11%
Native American
(North American Amerindian)
19%
Hispanic
(South or Central American)
14%
South Asian Indian12%
(14% express B*35:03)
Japanese17%
Chinese4%
Korean12%
Middle-Eastern, North African Coast13%
Filipino4%
(16% express B*35:05)

Phenotype frequency calculated from allele frequency assuming the Hardy-Weinberg proportions.  Data from allelefrequencies.net, USA NMDP data.

Your HLA-B Starting Point

Breaking old habits and forming new ones all starts with a single step. Take our HLA-B*35 Restricted CMV-Specific T Cells, for example. (Yes, we also have an HLA-A*02:01 Restricted line, if you insist.)

We generated this T cell line to be specific for a peptide from CMV bound to HLA-B*35. It produces IFNγ when stimulated with antigen-presenting cells (APC) and peptide. The cell line is also cytolytic to cells that express the appropriate antigen and HLA type, so you can use it to evaluate compounds for their ability to modulate cytotoxicity.

The figure below shows the sensitivity of these T cells to their antigen; they secrete IFNγ in the presence of only 100 pg/mL of peptide. 

Figure 1. 20,000 T cells were plated in a 96-well round-bottom plate with 20,000 donor 213 B-LCLs (expressing HLA-B*35) and either CMV pp65 peptide (IPSINVHHY) or EBV peptide (HPVGEADYFEY). After an overnight (18-24 hour) incubation period, supernatant was collected from each well. IFNγ concentration was analyzed using the Meso Scale Discovery IFNγ assay.

Leave a Reply

Your email address will not be published. Required fields are marked *

Post comment

This site uses Akismet to reduce spam. Learn how your comment data is processed.