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Antigenic variation can result from gene conversion, [1] site-specific DNA inversions, [2] hypermutation, [3] or recombination of sequence cassettes. [4] The result is that even a clonal population of pathogens expresses a heterogeneous phenotype. [5] Many of the proteins known to show antigenic or phase variation are related to virulence. [6]
Since most sequence variation associated with immunoglobulins and T cell receptors are found in the CDRs, these regions are sometimes referred to as hypervariable regions. [3] Within the variable domain , CDR1 and CDR2 are found in the variable (V) region of a polypeptide chain, and CDR3 includes some of V, all of diversity (D, heavy chains ...
This antigenic variation creates cyclical waves of parasitemia characteristic of Human African Trypanosomiasis. [ 5 ] Antigen 'cleaning' and VSG recycling—VSG is efficiently recycled through the trypanosome flagellar pocket, allowing antibodies to be 'cleaned' from VSG before re-incorporation back into the cellular membrane.
The human immune system relies on a plethora of cell-cell signaling pathways to transmit information about a cell's health and microenvironment. Many of these pathways are mediated by soluble ligands, cytokines, that fit like a lock-and-key into adjacent cell surface receptors.
The exogenous pathway is utilized by specialized antigen-presenting cells to present peptides derived from proteins that the cell has endocytosed. The peptides are presented on MHC class II molecules. Proteins are endocytosed and degraded by acid-dependent proteases in endosomes; this process takes about an hour. [1]
The process of V(D)J recombination is mediated by VDJ recombinase, which is a diverse collection of enzymes. The key enzymes involved are recombination activating genes 1 and 2 (RAG), terminal deoxynucleotidyl transferase (TdT), and Artemis nuclease, a member of the ubiquitous non-homologous end joining (NHEJ) pathway for DNA repair. [4]
The individual peptides are then complexed with major histocompatibility complex class II (MHC class II) molecules located in the lysosome – this method of "handling" the antigen is known as the exogenous or endocytic pathway of antigen processing in contrast to the endogenous or cytosolic pathway, [17] [18] [19] which complexes the abnormal ...
As a consequence, external soluble antigens are targeted into the MHC class I cross-presentation pathway instead of the MHC Class II pathway. [citation needed] However, there is still uncertainty in regard to a mechanistic pathway for cross presentation within an antigen presenting cell. Currently, there are two main pathways proposed ...