Human CD247 deficiency

  1. Ana Victoria Marín Marín
Supervised by:
  1. José Ramón Regueiro González-Barros Director
  2. George C. Tsokos Director

Defence university: Universidad Complutense de Madrid

Year of defence: 2020

  1. José Manuel Martín Villa Chair
  2. Miguel Fernández Arquero Secretary
  3. Clara Franco Jarava Committee member
  4. Diana Gil Pages Committee member
  5. Hisse Martien van Santen Committee member
  1. Inmunología, Oftalmología y ORL

Type: Thesis


The T-cell receptor (TCR) is the antigen receptor of T lymphocytes. In humans it is composed of one variable heterodimer (TCRαβ or γδ), two invariant heterodimers (CD3εγ and CD3εδ) and one invariant homodimer (CD247, also called ζζ). It has a crucial role during T-cell selection and activation, so that mutations in the genes codifying for TCR chains cause immunodeficiency disease (TCRID) of varying severity depending on the affected protein. TCRID cases are extremely rare but valuable models to understand human TCR biology, considering that mouse models or human genetically modified tumoral celllines do not fully recapitulate the behaviour of the human TCR. Our objectives were a) to characterize the T-cell phenotype of a new CD247-deficient patient and establish the pathognomonic features of the disease, and b) to study how homozygous or heterozygous mutations in CD247 affected the assembly and trafficking of the TCR from the endoplasmic reticulum (ER) to the T-cell surface as well as its recycling and degradation...