The Ecology of Humans (7-25) Major Histocompatibility Complex

 Major Histocompatibility Complex

Almost all human cells have protein-processed marker molecules called major histocompatibility complex (MHC). There are 2 classes of MHC molecule.

Class 1 MHC molecules are on all body cells except mature red blood cells. Class 2 MHC molecules are present only on certain cells, including macrophages, B cells, and dendritic cells. CD8 (killer T) cells bind to class 1 MHC, while CD4 (helper T) cells bind to class 2 MHC.

Helper T tag and flag infected cells for others to kill. Killer T directly attach to infected cells and kill them.

Each cell in the body comprises a network of microcanals (endoplasmic reticulum (ER)) that connect the cell cytoplasm and nucleus. Chromosomes inside the nucleus generate MHC molecules that range the ER and make it to the cell surface, acting as a signpost of self.

An invaded cell will display peptides attached to class 1 MHC that include processed pathogen proteins (proteasomes).

Both classes of MHC possess polymorphism: the ability to change shape. The number of forms that MHC proteins can take in humans runs to the hundreds. But an individual will have only a few types of class 1 or 2 MHC present on cells, and each cell has identical MHC types. MHC proteins are therefore a marker of individuality. That is why tissue transplants are so problematic.

T cells cannot recognize free-floating antigens. They can only recognize antigens when held by MHC molecules on the surfaces of other cells.

Use of MHC to identify fragments of foreign material allows T cells to identify pathogens that have altered their antigenic profile, and thus were able to slip past antibody identification. In the process of regenerating themselves, pathogens lose peptide particles which are picked up by MHC molecules and put on a T cell surface for identification.

T cell receptors are constructed by putting together several peptides, plus a few amino acid sequences. This combination allows the immune system to generate an almost infinite variety of receptors, capable of recognizing almost any potential invader.

Interaction between T and MHC is crucial for adaptive immune defense and has a long heritage: the same T–MHC mechanism is 450 million years old, developed in the common ancestor to frogs, trout, sharks, and people.