peptide MHC microarray

Question

"The recent technology is peptide–MHC microarray or artificial antigen-presenting chip. In this technique, recombinant peptide–MHC complexes and co-stimulatory molecules are immobilized on a surface, and population of T cells is incubated with the microarray. The T cell spots act as artificial antigen-presenting cells containing a defined MHC-restricted peptides. The advantage of using peptide–MHC is that it can map MHC-restricted T cell epitope."

These few lines are from Chapter 3 of Immunoinformatics, De, Rajat K., Tomar, Namrata (Eds.).

What is recombinant peptide MHC? What is MHC restricted peptide? How did the advantage get derived?

Answer 1

According to this paper (Yoav Soen et al. PLoS Biology 2003), peptide:MHC microarrays are a type of cellular microarray (a microarray designed to identify cell types; Wikipedia). These microarrays have attached a MHC molecule bound to a peptide, which allows them to work as artificial antigen presenting cells (APCs) that activate specific subpopulations of T cells.

Another recent paper is here where they specifically use the word recombinant peptide:MHC.

The expression MHC restricted refers to the positive selection (in the thymus) of T cells that recognize MHC molecules of the host but not other self-antigens (Wikipedia).

Answer 2

This is an important topic in immunology, especially for vaccine development.

MHC or HLA is a molecule expressed by some cells of the immune system which acts like a "catcher's mitt" and "presents" short snippets of protein to other immune cells. Other molecules act alongside MHC to provide co-signals which promote or suppress immune attack against the peptides that MHC presents.

Basically, it's a protein that holds out chunks of other proteins in order to educate the rest of the immune system. Here's the catch: different people have different genes for MHC which do a better or worse job of presenting certain peptides. This is one reason why different people can respond to different vaccines or different pathogens or cancers: they have different MHCs which may or may not present peptides from the relevant targets.

Thus, one big challenge in medicine right now is to develop good models for which peptides are best to include in a vaccine. The right answer depends on the genetics of the vaccine target (ebola, a tumor, e. coli etc) and also on the genetics of the person being vaccinated (does this person's MHC gene properly present this vaccine?)

So, to datafy this, people sometimes make arrays which allow us to quantify which peptides bind to which MHC genes in high throughput. Then we can use that data to learn which factors are most important for P:MHC binding. "MHC restricted" means that we are talking about a specific genetic subtype of these molecules.

Hope that helps. Bion Alex Howard