T Dependent (TD) Antigens

Ø  T Dependent (TD) Antigens require the participation of T lymphocytes for the stimulation of B cells to produce Abs. T cells are of two types. Helper T cells (T_H) or CD 4+ cells and cytotoxic T cells (T_C) or CD 8+ cells. T_H cells are involved in B cell activation by TD antigens.

Ø  TD antigens are structurally complex molecules like serum proteins, protein-hapten complex, erythrocytes etc. Activation of B cells by TD antigens is more complex, but results in stronger response with immunological memory. TD antigens have to be first processed by the An processing/ presenting cells (APC).

Ø  Macrophages, dendritic cells and B cells usually act as An processing/presenting cells. These cells capture An and present them to T lymphocytes. APCs have 2 unique properties.

1.      They express MHC Class II molecules on their surface.

2.      They can also produce co-stimulatory signals necessary to activate T_H cells

APCs first internalize the An by phagocytosis or endocytosis. Then APCs display part of An bound to MHC Class II molecules on their surface membrane.  T_H cells can recognise only those Ans that are presented or attached to MHC class II.

·         I signal - If B cell is acting as the APC, then the first signal is binding of An and BCR. B cell will then internalise the An, process it and present part of An on it surface along with MHC Class II which will be recognized by  T_H cells.

·         II signal - T Cell Receptor (TCR)-CD3 complex on the surface of T Cell recognize and bin to the MHC Class II + An expressed on the surface of B cells. CD4 molecule of T cell also bind to a specific portion on the MHC molecule of B cell to make the binding more  effective. This binding of B cell/APC to T_H cell is called “linked recognition”.

Ø  Additional activation of T_H cells are brought about co-stimulatory signals produced by the APCs. A number of co-stimulatory molecules are involved in T cell activation.  

Co-stimulatory signals

·      CD 28 on T_H cells binds to CD 80 (B7-1) or CD86 (B7-2) membrane proteins on APC. This interaction will activate the T_H cells to secrete various cytokines.

·       T_H cells also start expressing CD40 Ligand (CD40L) which will interact with complementary CD40 of the B cell. This interaction is essential for the survival of B cells and also for germinal centre formation for the secretion of memory cells.

Ø Activated T_H cells secrete T cell growth factor or Interleukin-2 (IL-2) which will act on the T_H cell itself and initiate its proliferation. Proliferated T_H cells are called naïve T cells or T_H0 cells.

Ø Proliferated T_H cells secrete IL-2, IL-4, IL-5, IFN-γ etc. B cells begin to express receptors for various cytokines, bind to cytokines released by T_H cells and thus B cells get activated.

Ø The activated B-cell clonally proliferates to produce a population of plasma cells (Effector B cells) and secrete Abs against the An which had initiated all these process. Initially IgM are the Abs produced by plasma cells. After several rounds of proliferation, B cells differentiate to form memory B cells which will act during secondary response.   

Ø After initial secretion of IgM, cytokines secreted by T_H2 cells stimulate the plasma cells to switch from IgM production to production of IgG, IgA, or IgE. This process is called class switching or isotype switching. By class switching, plasma cells produced from the same B cell could produce a variety of antibody classes with the same epitope specificity. Class switching is due to genetic rearrangement of gene segments encoding the constant region of Abs which determines the antibody type or class.

Ø Differences between TI & TD Antigens

TI Antigens	TD Antigens
Structurally simple & composed of limited number of repeating epitopes	Structurally complex
Molecules like bacterial capsular polysaccharides, bacterial lipopolysaccharides and  some polymeric proteins like flagellar protein flagellin	Molecules like serum proteins, protein-hapten complex, erythrocytes etc
Immune response is dose dependent. Too little An is non- immunogenic & too much An cause immunological tolerance	Immunogenic over wide dose range. Do not readily cause tolerance
Do not require preliminary processing by APCs	Require preliminary processing by APCs and presented along with MHC class II molecules on the surface of APC
Ab response limited to IgM and no isotype switching	Isotype switching occurs and induce formation of almost all isotypes like IgM, IgG, IgA &IgE
Week response & no immunological memory	Strong response with immunological memory
Metabolized slowly and remain in body for long periods	Metabolized rapidly in the body