Nurse shark T-cell receptors employ somatic hypermutation preferentially to alter alpha/delta variable segments associated with alpha constant region.
Eur J Immunol
; 50(9): 1307-1320, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32346855
ABSTRACT
In addition to canonical TCR and BCR, cartilaginous fish assemble noncanonical TCR that employ various B-cell components. For example, shark T cells associate alpha (TCR-α) or delta (TCR-δ) constant (C) regions with Ig heavy chain (H) variable (V) segments or TCR-associated Ig-like V (TAILV) segments to form chimeric IgV-TCR, and combine TCRδC with both Ig-like and TCR-like V segments to form the doubly rearranging NAR-TCR. Activation-induced (cytidine) deaminase-catalyzed somatic hypermutation (SHM), typically used for B-cell affinity maturation, also is used by TCR-α during selection in the shark thymus presumably to salvage failing receptors. Here, we found that the use of SHM by nurse shark TCR varies depending on the particular V segment or C region used. First, SHM significantly alters alpha/delta V (TCRαδV) segments using TCR αC but not δC. Second, mutation to IgHV segments associated with TCR δC was reduced compared to mutation to TCR αδV associated with TCR αC. Mutation was present but limited in V segments of all other TCR chains including NAR-TCR. Unexpectedly, we found preferential rearrangement of the noncanonical IgHV-TCRδC over canonical TCR αδV-TCRδC receptors. The differential use of SHM may reveal how activation-induced (cytidine) deaminase targets V regions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tiburones
/
Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T
/
Cadenas Pesadas de Inmunoglobulina
/
Reordenamiento Génico de la Cadena alfa de los Receptores de Antígenos de los Linfocitos T
/
Citidina Desaminasa
/
Hipermutación Somática de Inmunoglobulina
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos