MHC I / T-Cell Interactions
Most Cytotoxic T-Lymphocytes (CD8+ Cells) possess both T-Cell Receptors (TCR) and CD8+ molecules (as well as many other proteins) on their surfaces.
These TCRs are able to recognize Peptides, but only when they are expressed in complexes with MHC I molecules. In order for the TCR to bind a Peptide-MHC complex two requirements must be met:
- The TCR must have a structure which allows it to bind the Peptide-MHC complex
- The accessory molecule CD8+, must bind to the alpha-3 domain of the MHC Class I molecule
Due to Genetic recombination events, each T-Cell expresses a unique TCR, which will only bind a specific MHC-Peptide complex.
T-Cells that recognize Self-Peptides are eliminated in the Thymus or Tolerized by an unknown mechanism, after their release from the Thymus.
As a result, if a T-Cell is able to bind to a MHC-Peptide complex on the surface of a cell, this cell is producing a Peptide which is not native to the person.
If this occurs, the CD8+ Cell separates from the invaded cell, grows (differentiate), and divides (Colonal Expansion).
This, and the subsequent development into a mature CD8+ Cell, requires more Cytokines (notably, InterLeukin-2 from CD4+ Cells).
However once differentiated, the T-Cell and its progeny will eliminate any cells expressing the same Peptide-MHC complex, which activated the original CD8+ Cell.
In addition, some of the progeny will become dormant Memory T-Cells. Though poorly understood, these cells stay in a resting state, until encountering the Peptide-MHC complex they recognize (e.g. during a re-infection with the same Antigen), whereupon they become mature CD8+ Cells.
The MHC I molecule acts as a means of assuring that self cells, have not been compromized by infection or mutation.
Any cell which is hosting a Virus or manufacturing mutant proteins (as in the case of Cancer) will present these foreign Peptides upon its surface. A CD8+ Cell will recognize them and eventually the cell will be destroyed.
MHC II / Helper T-Cell Interactions
The Helper T-Cells (CD4+ aka [Th Cell]) is responsible for regulating almost every Acquired Immune System activity.
The signaling molecules on its membrane and the Cytokines it produces are necessary for the development of most Acquired Immune Responses.
Just as CD8+ Cells must interact with MHC I, Helper T-Cells must contact a MHC II-Peptide complex, which they recognize, in order to be activated. Instead of CD8, Helper T-Cells, have a molecule called CD4, which binds to MHC II.
As in the case of CD8+ Cells, self-reactive cells are destroyed in the Thymus or Tolerized in the periphery, so if a Peptide is recognized, it is probably of foreign origin.
Assuming the APC which presented the MHC II-Peptide, also possessed a surface molecule or Cytokine which acted to co-stimulate the CD4+, the cell will produce Cytokines to allow its own maturation and propagation.
These CD4+ Cells will then proceed to supply the necessary Cytokines for Immune Responses against Antigen they recognize. Both Humoral and Cytotoxic Immunity are seriously hindered without this support.
In some cases, as in the Immune Response to Tuberculosis, the CD4+ Cells activation of the Innate Immune System is the Primary Immune Response.
As with CD8+ Cells, a portion of CD4+ Cells are Memory Cells, which remain dormant until a reinfection occurs.