Most antigens are materials foreign to the body. T- and B-lymphocytes are both primed during maturation to be able to recognise specific antigens, even though they may never encounter that antigen.

Considering that there are literally millions upon millions of potential antigens, it used to be a mystery how the immune system could prepare so many lymphocytes. It is now known that in the thymus gland and the bone marrow the genetic code of lymphocytes antigen receptors is randomly rearranged to create enough variations in antibody and T-cell receptors that may be required during life. So for each specific antigen encountered during life, there will be at least several T- and B-cells existing to recognise the antigen and set off a specific immune response. These activated lymphocytes will then increase in number establishing immune memory, constituting acquired immunity.

T-cells are primed to weakly recognise 'self molecules called major histocompatibility complex (MHC) molecules. This priming occurs during their maturation. T-lymphocytes that strongly recognise MHC molecules are eliminated, since these cells would recognise self and do damage to the body.

Unlike B-cells, T-cells only recognise specific antigens when they are 'presented to them with an MHC molecule. So the recognition of antigen by T-cells is done in conjunction with recognising a 'self' molecule. This increases the weak recognition of MHC to a strong recognition because of the presence of foreign antigen, leading to initiation of the immune response. The main presenting cells are dendritic cells, and less often, macrophages. One type of MHC molecule (class I) contains a protein called beta-2 microglobulin which is released from activated or killed cells including lymphocytes. It can be measured in blood as a marker of immune activation.

MHC molecules are hugely genetically diverse and it is incredibly unlikely that two unrelated people will have the same collection of MHC molecules on the surface of their cells. It seems likely that the efficiency of the immune system in dealing with antigens varies by the type of MHC molecules we carry. Lymphocytes react strongly to other people's MHC molecules as being foreign which is why matching for tissue type is so important to stop rejection of transplanted organs.

Human leukocyte antigens (HLAs)

The human MHC molecules are also known as human leukocyte antigens (HLAs). There are two main classes of HLA.

Class I is divided into HLA A, B and C which are expressed by most human cells. Class I HLA presents antigen to CD8 T-cells, leading to CD8 T-cell activation. When CD8 T-cells recognise antigen presented by HLA class I, they kill the cell presenting it. This is how CD8 T-cells destroy cells infected with viruses, including HIV. The genetic make-up of a person's HLA probably affects the efficiency of their response to viruses and is known to affect the rate of HIV disease progression.

Class II is divided into HLA DP, DQ and DR which are expressed by cells such as macrophages and dendritic cells. See Immune cells in The immune system and HIV: How the immune system works for more details. Class II HLA presents antigen to CD4 T-cells, thus activating them. When CD4 T-cells strongly recognise antigen presented by HLA class II, they secrete chemical messengers called cytokines which further stimulate the immune response.