What is the Difference Between Positive and Negative Selection of T Cells

The key difference between positive and negative selection of T cells is that in the positive selection, the double-positive T cells bind to cortical epithelial cells expressing Class I or Class II MHC, while in negative selection, double-positive T cells bind to bone-marrow-derived antigen-presenting cells.

The development of T cells is an important process in the immune system. The development process takes place in the thymus and has two main pathways as positive selection and negative selection pathways. Both are mediated by specific signals that play a role in the development procedure of  T cells.

CONTENTS

1. Overview and Key Difference
2. What is Positive Selection of T Cells
3. What is Negative Selection of T Cells
4. Similarities – Positive and Negative Selection of T Cells 
5. Positive vs Negative Selection of T Cells in Tabular Form
6. Summary – Positive vs Negative Selection of T Cells 

What is Positive Selection of T Cells?

Positive selection takes place in the thymic cortex. This is a process where thymocytes form the double-positive T cells. They migrate into the thymus, resulting in the presentation of self-antigens. These self-antigens are associated with the Major Histocompatibility Complex (MHC). The T cells that react with MHC-I and MHC-II will gain the ability to survive. The positive selection of T cells thus results in initiating the immune response. This process takes a number of days, and some T cells undergo destruction during it.

Moreover, the positive selection also determines whether the T cell will become a helper or a cytotoxic T cell. Positive selection on Class I MHC will produce a CD8 cytotoxic T cell, while positive selection on Class II MHC will yield a CD4 T helper cell. The process of positive selection of T cells will not remove the T cells that would lead to autoimmunity.

What is Negative Selection of T Cells?

The negative selection of T cells takes place in the medulla of the thymus. Thymocytes that show double positive nature (CD4+/CD8+) will undergo negative selection. The cells are presented with antigens by medullary thymic epithelial cells or antigen-presenting cells such as macrophages or dendritic cells. Thus, some epithelial cells undergo phagocytosis, leading to the negative selection between the binding of MHC class I peptides and MHC class II peptides. During the negative selection of T cells, CD4+ cells interact with MHC Class II molecules, and CD8+ cells interact with MHC class II molecules. In addition, the negative selection also results in death signals, provided the interaction of the thymocytes and the self-antigens are too strong.

Furthermore, the negative selection also prevents the formation of self-reactive T cells that are capable of giving rise to autoimmune diseases. At the end of the negative selection process, T cells that leave the thymus will possess three main features leading to the formation of self-restricted, self-tolerant, and single-positive T cells.

What are the Similarities Between Positive and Negative Selection of T Cells?

• Both play an important role in mediating adaptive immune responses.
• They are involved in the development and maturation process of T cells.
• Moreover, both selection processes take place in the thymus.
• Presentation of self-antigens is a common occurrence in both processes.
• Both are essential to maintain the immune system in the correct functionality.

What is the Difference Between Positive and Negative Selection of T Cells?

The key difference between positive and negative selection of T cells is based on how the antigen presentation takes place. In the positive selection of T cells, the antigen presentation takes place directly via the association between MHC class I and class II, resulting in double-positive T cells. In contrast, during the negative selection of T cells, antigen-presenting cells like macrophages incorporate the antigens to the T cells. In a natural context, negative selection takes place after positive selection. Even though both take place in the thymus, the region of the thymus where each process takes place is different. Moreover, positive selection takes place in the cortex, while negative selection takes place in the medulla.

Besides, the negative selection also activates death signals and activates apoptosis. This feature is not present in positive selection. Furthermore, the negative selection also can prevent the production of cells that are capable of self-reacting. This minimizes the risk of autoimmune responses.

The below infographic presents the differences between positive and negative selection of T cells in tabular form for side by side comparison.

Summary – Positive vs Negative Selection of T Cells

Positive and negative selections of T cells are two essential processes in the T cell development pathway that takes place in the thymus. While positive selection takes place in the thymic cortex, negative selection takes place in the thymic medulla. The key difference between positive and negative selection of T cells is based on the association of the T cell with the antigen presentation. In positive selection, double-positive cells associated with MHC class I and II are created. In contrast, during negative selection, antigen-presenting cells such as dendrites impart antigens onto the T cell. So, this summarizes the difference between positive and negative selection of T cells.

Reference:

1. Decker, Janet M. “T Cell Development“. Northern Arizona University.
2. Starr, TK, et al. “Positive and Negative Selection of T Cells.” Annual Review of Immunology, U.S. National Library of Medicine.

Image Courtesy:

1. “2217 Differentiation of T Cells Within the Thymus” By OpenStax College – Anatomy; Physiology, Connexions Web site. Jun 19, 2013. (CC BY 3.0) via Commons Wikimedia
2. “T cell negative selection” By Immcarle64 – Own work (CC BY-SA 4.0) via Commons Wikimedia