Platelets Present Antigen in the Context of MHC Class I

Abstract

Platelets are most recognized for their vital role as the cellular mediator of thrombosis, but platelets also have important immune functions. Platelets initiate and sustain vascular inflammation in many disease conditions, including arthritis, atherosclerosis, transplant rejection, and severe malaria. We now demonstrate that platelets express T cell costimulatory molecules, process and present Ag in MHC class I, and directly activate naive T cells in a platelet MHC class I-dependent manner. Using an experimental cerebral malaria mouse model, we also demonstrate that platelets present pathogen-derived Ag to promote T cell responses in vivo, and that platelets can be used in a cell-based vaccine model to induce protective immune responses. Our study demonstrates a novel Ag presentation role for platelets.

Nouvelle Cuisine: Platelets Served with Inflammation

“…It now appears that, in syngeneic systems, activated platelets can express nascent MHC class I molecules, and these have the ability to present Ags to CD8 + T cells. Chapman et al (76) elegantly demonstrated that activated platelets can present malarial peptides to malaria-specific T cells, and this leads to an enhanced immunity against the parasite. Thus, depending on the source of MHC (surface bound or internalized), platelets can mediate either T cell suppression or activation.…”

Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling

“…Platelets are often called antigen presenting cells (APCs) as they activate T cells through pMHCI 78. The pMHCI is constitutively expressed by platelets and their expression increases significantly during inflammation 79…”

Role of Platelet-Mediated Cytoadherence and Chemokines Release in Severe Malaria

“…We have also performed studies showing that CXCL4-/-mice have reduced mortality from CM [4]. Damage caused by CXCL4 progresses through T-Cell and monocyte activation and migration resulting into BBB breakdown [19][20][21], which in turn also results in increased permeability of cerebral micro-capillaries. Other groups have also demonstrated that T-Cell activation is an important step in CM progression [22].…”

“…We have demonstrated that the CXCL4 participates in the progression of CM. Also, CXCL4-mediated cerebral damage is accompanied by T-Cell and monocyte activation plus consequent BBB breakdown [18][19][20][21]. Both platelets and monocytes can release the cytokines upon the onset of CM.…”