The adaptive immune system relies on two central players: T cell receptors (TCRs) and antibodies, each capable of recognizing an immense variety of antigens. 
 
𝗧 𝗖𝗲𝗹𝗹 𝗥𝗲𝗰𝗲𝗽𝘁𝗼𝗿𝘀 (𝗧𝗖𝗥s): 
TCRs are heterodimeric proteins on the surface of T cells that recognize peptide antigens presented by MHC molecules. The combinatorial diversity of TCRs arises from: 
• V(D)J recombination: random recombination of variable (V), diversity (D), and joining (J) gene segments. 
• Junctional diversity: addition or deletion of nucleotides at gene segment junctions. 
• α and β chain pairing: each T cell expresses a unique combination of α and β chains. 
 
Mathematically, the potential TCR repertoire in humans is estimated to exceed 10¹⁵ unique receptors, enabling T cells to recognize any peptide-MHC complex [1][2]. For example, a single T cell clone specific for a viral peptide can expand dramatically upon infection, while billions of other unique TCRs remain poised for new threats. 
 
Antibodies:
Antibodies are secreted by B cells and can neutralize pathogens, opsonize cells for phagocytosis, or trigger complement activation. Their diversity comes from: 
V(D)J Recombination:
• Somatic hypermutation – point mutations introduced in the variable regions during B cell maturation to increase affinity. 
• Class switching – changing the constant region to shift effector functions (IgG, IgA, IgM, IgE, IgD). 
 
Combinatorial diversity allows the immune system to generate millions of different antigen-binding sites, each capable of recognizing a distinct epitope. For example, BiTes or engineered TCRs can combine this diversity to target multiple tumor antigens simultaneously. 
 
𝗔𝗽𝗽𝗹i𝗰𝗮𝘁𝗶𝗼𝗻𝘀 𝗶𝗻 𝗜𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝘆: 
• TCR-engineered T cells: Target tumor-specific peptides presented by MHC. 
• Monoclonal antibodies: Used in checkpoint inhibition, neutralization of pathogens, or targeted delivery of cytotoxic agents. 
• Bispecific antibodies and TCR-mimics: Combine specificity from multiple sources for enhanced targeting of heterogeneous tumors. 
 
𝗥𝗶𝗱𝗱𝗹𝗲 𝗳𝗼𝗿 𝘁𝗵𝗲 𝗔𝘂𝗱𝗶𝗲𝗻𝗰𝗲: 
How does the immune system detect new antigens from unknown organisms, if we are discovering new species every day? (There are no right and wrong answers) 
 
Stay tuned for 𝗗𝗮𝘆 𝟴𝟲: 𝗠𝗼𝘀𝘁 𝗻𝗼𝘁𝗮𝗯𝗹𝗲 𝗶𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝘆 𝗰𝗹𝗶𝗻𝗶c𝗮𝗹 𝘁r𝗶𝗮𝗹s
 
References:
1. DOI:10.1038/334395a0 
2. DOI: 10.1182/blood-2009-04-217604 
3. DOI:10.1016/j.jaci.2009.09.046 
 
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