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T Cell Activation and Clonal Selection

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...

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Related Experiment Video

Updated: Aug 31, 2025

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Published on: March 28, 2025

Carbon source availability drives nutrient utilization in CD8⁺ T cells.

Irem Kaymak¹, Katarzyna M Luda², Lauren R Duimstra¹

¹Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.

Cell Metabolism

|August 18, 2022

Summary

This summary is machine-generated.

Nutrient availability profoundly impacts CD8+ T cell metabolism. Lactate, not glucose, fuels T cells during infection, enhancing their function and survival.

Keywords:

(13)C tracing T cells TCA cycle immunometabolism lactate metabolic programming metabolomics

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Area of Science:

Immunology
Cell Metabolism
Nutrient Sensing

Background:

T cell metabolism is crucial for immune responses.
Environmental nutrient availability's role in T cell function is not fully understood.
The impact of physiologic carbon sources (PCSs) on CD8+ T cell metabolism requires further investigation.

Purpose of the Study:

To investigate how environmental nutrient availability influences CD8+ T cell metabolism and function.
To determine the role of physiologic carbon sources (PCSs) in CD8+ T cell glucose utilization.
To identify alternative metabolic fuels for CD8+ T cells.

Main Methods:

Culturing CD8+ T cells in the presence and absence of PCSs.
Measuring glucose utilization and TCA cycle contribution.
Assessing effector function and bioenergetic capacity.
Inhibiting lactate dehydrogenase A (Ldha) to study lactate metabolism.
Evaluating T cell metabolic homeostasis and proliferation in vivo.

Main Results:

PCSs broadly impacted glucose utilization by CD8+ T cells, independent of transcriptional changes.
PCSs reduced glucose contribution to the TCA cycle and enhanced effector function.
Lactate directly fueled the TCA cycle, serving as a preferred substrate over glucose for T cells during Listeria infection.
Lactate enhanced T cell bioenergetic and biosynthetic capacity.
Inhibiting Ldha impaired T cell metabolic homeostasis and in vivo proliferation.

Conclusions:

Environmental carbon source availability shapes T cell glucose metabolism.
Lactate serves as a critical bioenergetic and biosynthetic fuel for CD8+ effector T cells.
Targeting lactate metabolism could be a strategy to modulate T cell immunity.