Identifying Haplotypes of Different Mouse Strains Using Mhc Restriction and Cytotoxic T Cells

Identifying haplotypes of different mouse strains using MHC restriction and cytotoxic T cells.

Introduction

The immune system is very accomplished in keeping our body safe, and a key player is the Major Histocompatibility Complex (MHC). There are two classes of MHC, class I and class II, and are located on the cell surface of the non-antigen presenting cells and antigen presenting cells, respectively. MHC molecules are a means for the immune cells such as T cells, to communicate with other cells of the body that have been infected with a pathogen such as a virus, or that are specifically designed to present pathogen associated molecular patterns. When a non-self antigen enters the internal environment of the body, it can get engulfed and digested into peptides by macrophages. Therefore, cell-mediated immunity relies on a mechanism known as MHC restriction that ensures only cells that are required to die, to be killed (2). MHC restriction means the T cell will only be activated when the peptide of the non-self antigen is bound to an MHC molecule. The T cell must be able to recognize both the MHC and the peptide to initiate a response. Recognition of only one will not initiate a response (3). When T cells are developing in the thymus, they are filtered, so that T cells have an intermediate affinity for peptides on the MHC, as is shown in figure 1. Too low, and the body will not have an effective response to antigens, and too high, the body is likely to develop autoimmune diseases. Peter Doherty and Rolf Zingernagel, who were awarded a Nobel Prize for Physiology or Medicine in 1996, discovered these interactions between T cells with MHC. (1)

Figure 1: Image showing no recognition between t cell receptor and MHC receptor (left), low to moderate recognition (middle) and high recognition (right). Source:  Nature reviews

[pic 1]

Results

Table 1: Raw data displaying the assay values.

Figure 2: Graph representing the mean cytotoxicity from different mouse strains and concentration. [pic 2]

Table 2: Analysis of raw data

To test the MHC restriction, several strains of mice were infected with the MSV virus. The target mouse produced T cells that was able to fight the MSV virus, and it had the haplotypes db. We infected other strains of mice with the MSV virus and then observed if the T-cells lysed the infected cells of the other mice.